Fluorine has become an increasingly important element in modern pharmaceutical chemistry. Introducing fluorine or fluorinated functional groups into a molecule can significantly influence its lipophilicity, metabolic stability, molecular conformation, and biological properties.

However, forming a carbon–fluorine bond within a complex molecule is often synthetically challenging. This is why efficient and selective fluorinating reagents remain essential tools in pharmaceutical and specialty chemical synthesis.

Diethylaminosulfur trifluoride, commonly abbreviated as DAST, is one of the best-known nucleophilic fluorinating reagents used for this purpose.

With CAS No. 38078-09-0, DAST is also known as (Diethylamino)sulfur trifluoride and N,N-Diethylaminosulfur trifluoride. Its molecular formula is C₄H₁₀F₃NS, with a molecular weight of 161.19 g/mol. PubChem identifies DAST as a fluorinating agent and lists CAS 38078-09-0 among its principal identifiers.

DAST is particularly useful for converting alcohols into alkyl fluorides and for transforming aldehydes and ketones into geminal difluorides. It has also been applied to the synthesis of fluorinated pharmaceutical intermediates, including intermediates associated with Belzutifan, 5,5-difluoropipecolic acid, fluorinated carbazole-piperazine derivatives, and complex natural-product intermediates.

1. What Is Diethylaminosulfur Trifluoride?

Diethylaminosulfur trifluoride is an organosulfur fluorinating reagent belonging to the family of dialkylaminosulfur trifluorides.

Its commonly used identifiers include:

PubChem confirms the molecular formula C₄H₁₀F₃NS, molecular weight 161.19 g/mol, and CAS No. 38078-09-0.

Commercial technical data report DAST as a colorless to yellow or orange liquid, with density around 1.22 g/mL at 25°C and a refractive index around 1.41–1.416.

Because DAST is highly moisture-sensitive and reactive, physical-property values should be regarded as reference data; the current supplier specification and Certificate of Analysis should be used for batch-specific quality assessment.

2. Why DAST Is an Important Fluorinating Reagent

The primary value of DAST comes from its ability to provide fluoride for nucleophilic fluorination.

In a simplified way, DAST can activate a suitable functional group while providing fluoride for the formation of a new C–F bond.

One of its best-known transformations is:

Alcohol → Alkyl fluoride

It can also be used for:

Aldehyde or ketone → Geminal difluoride

This reaction flexibility has made DAST an important reagent in synthetic organic chemistry.

TCI describes DAST as a fluorinating reagent and provides an example of converting an alcohol into the corresponding fluoride.

Sigma-Aldrich likewise describes DAST as a widely used nucleophilic fluorinating reagent applicable to alcohols, alkenols, carbohydrates, ketones, sulfides, epoxides, thioethers, and cyanohydrins.

3. From Alcohols to Fluorinated Pharmaceutical Intermediates

One of the most important applications of DAST is the transformation of alcohol functionality into fluorinated products.

The general concept is:

R–OH → R–F

This transformation can be valuable when the final target molecule requires a fluorine atom at a position originally occupied by a hydroxyl group.

For pharmaceutical chemistry, this is particularly useful because fluorine substitution can alter molecular properties without substantially increasing molecular size.

Depending on the substrate, fluorination can influence:

• · Lipophilicity
• · Metabolic stability
• · Hydrogen-bonding behavior
• · Molecular conformation
• · Electronic properties
• · Biological activity

As a result, fluorination has become a standard strategy in medicinal chemistry and pharmaceutical development.

DAST provides one practical route for introducing fluorine into appropriately functionalized molecules.

4. DAST for the Synthesis of Gem-Difluorides

DAST is not limited to simple alcohol-to-fluoride conversion.

Another important transformation is the conversion of carbonyl compounds into geminal difluorides.

For suitable aldehydes or ketones, DAST can replace the carbonyl oxygen environment with two fluorine atoms at the same carbon.

Conceptually:

C=O → CF₂

This transformation is particularly valuable when developing fluorinated building blocks.

Gem-difluoromethylene groups can serve as useful bioisosteric or conformationally modifying units in medicinal chemistry.

The ability of DAST to perform both alcohol fluorination and carbonyl difluorination contributes significantly to its versatility.

5. Application in the Synthesis of 5,5-Difluoropipecolic Acid

One of the specific applications associated with DAST is the synthesis of 5,5-difluoropipecolic acid, also known as 5,5-difluoropiperidine-2-carboxylic acid.

This compound is an important fluorinated amino-acid-type building block for medicinal and synthetic chemistry.

Sigma-Aldrich’s technical information specifically describes DAST-mediated fluorodeoxygenation in the preparation of 5,5-difluoropipecolic acid from glutamic acid.

This example illustrates an important advantage of DAST:

Rather than introducing fluorine into a simple model molecule, the reagent can be incorporated into a synthetic strategy for preparing structurally useful fluorinated intermediates.

Such compounds can subsequently be used for the preparation of more complex pharmaceutical structures.

6. DAST and Belzutifan Intermediate Synthesis

Belzutifan, marketed as Welireg™, is a fluorine-containing pharmaceutical compound and a HIF-2α inhibitor.

The structure of belzutifan contains three fluorine atoms and multiple stereogenic centers. PubChem and the U.S. National Library of Medicine’s chemical resources identify its molecular structure and stereochemistry.

DAST has been reported in synthetic studies involving fluorinated intermediates relevant to belzutifan.

A published review of fluorine-containing drugs describes a synthetic sequence in which a stereoselective fluorination of an alcohol intermediate using (diethylamino)sulfur trifluoride (DAST) produced a vicinal difluoro compound.

This makes DAST relevant to the broader development history of fluorinated intermediates associated with belzutifan.

However, it is important to distinguish published synthetic routes from the final commercial manufacturing process.

Merck’s later process-development work on belzutifan reported alternative fluorination chemistry and focused extensively on process safety, stereochemical control, scalability, and robustness.

For an E-E-A-T-focused chemical website, this distinction matters.

A technically accurate statement is therefore:

DAST has been reported as a fluorinating reagent in synthetic studies toward belzutifan and related fluorinated intermediates.

This is more precise than claiming that DAST is necessarily the fluorinating reagent used in the current commercial manufacturing process.

7. DAST in Fluorinated Carbazole-Piperazine Chemistry

Another interesting application of DAST involves the preparation of fluorinated carbazole-piperazine derivatives.

These compounds have been investigated as modulators associated with the Bax channel and cytochrome c release pathways.

Literature summarized by Sigma-Aldrich describes the use of DAST to obtain fluorinated analogues of 3,6-dibromocarbazole piperazine derivatives.

An academic review likewise reports that DAST was used to prepare fluorinated analogues of carbazole-piperazine derivatives that were investigated as potent modulators of cytochrome c release triggered by Bid-induced Bax activation.

This application demonstrates how DAST can be used in medicinal chemistry research to introduce fluorine into relatively complex heterocyclic structures.

8. DAST in Ciguatoxin-Related Synthesis

DAST also has a place in the synthesis of complex natural-product intermediates.

One notable example is the preparation of fluorinated intermediates related to ciguatoxins.

Ciguatoxins are structurally complex marine natural products containing multiple rings and stereochemically defined functional groups.

In synthetic chemistry, fluorinated sulfide intermediates can be useful building blocks for assembling these complex structures.

Published synthetic literature describes the use of DAST together with a catalyst to convert a hydrogen-containing precursor into a fluorinated sulfur-containing intermediate relevant to ciguatoxin synthesis.

This is another example of DAST’s value beyond conventional pharmaceutical intermediate chemistry.

Its applications extend into complex molecule and natural-product synthesis, where selective fluorine introduction can provide a valuable synthetic handle.

9. Why Fluorination Is Important in API Development

The pharmaceutical industry’s interest in fluorinated compounds is not accidental.

Fluorine can influence the behavior of a molecule in several ways.

Lipophilicity

Fluorine substitution can modify the hydrophobic character of a molecule.

Metabolic Stability

Certain C–F bonds can reduce susceptibility to metabolic oxidation at specific molecular positions.

Electronic Effects

Fluorine is strongly electron-withdrawing and can change the electronic environment of neighboring functional groups.

Conformation

Fluorination can affect molecular conformation and intramolecular interactions.

Biological Activity

Changes in molecular properties can influence receptor binding, enzyme inhibition, and other pharmacological characteristics.

For this reason, fluorinated structures are common throughout modern medicinal chemistry.

DAST is one of the reagents that allows synthetic chemists to introduce these fluorinated motifs.

10. DAST Compared with Other Fluorinating Reagents

DAST is not the only reagent used for organic fluorination.

Depending on the substrate and process requirements, chemists may consider reagents such as:

• · Deoxo-Fluor
• · XtalFluor-type reagents
• · Selectfluor
• · Sulfur tetrafluoride-derived systems
• · Other nucleophilic fluorinating reagents

The correct reagent depends on:

• · Functional-group compatibility
• · Required selectivity
• · Reaction temperature
• · Substrate sensitivity
• · Scale
• · Safety profile
• · Process economics
• · Waste treatment requirements

DAST’s main advantage is its broad and well-established reactivity.

However, high reactivity also creates additional process-safety considerations.

For commercial pharmaceutical manufacturing, the reagent that works well on laboratory scale is not necessarily the reagent ultimately selected for large-scale production.

11. Physical Properties and Safety Considerations

DAST should not be treated as an ordinary laboratory solvent or general-purpose reagent.

It is a highly reactive, moisture-sensitive fluorinating reagent.

Available technical information reports a density of approximately 1.22 g/mL at 25°C, a refractive index around 1.410–1.416, and a flash point near 23°C.

DAST reacts with moisture and water, producing hazardous fluorinated decomposition products including hydrogen fluoride.

Commercial safety information identifies it as a hazardous material capable of causing severe skin burns and eye damage. It is also classified as flammable.

Consequently, DAST should be:

• · Kept away from moisture
• · Stored according to the current SDS
• · Handled by trained personnel
• · Used with suitable engineering controls
• · Protected from incompatible materials
• · Transported and packaged according to applicable regulations

SHLZ Pharma’s published product information recommends storage at 2–8°C, under nitrogen protection, in a dry environment.

The exact storage and shipping requirements should always be determined from the latest product SDS and applicable regulations.

12. Why Moisture Control Is Critical

The sensitivity of DAST to moisture has direct implications for product quality.

Water can react with the reagent and reduce its effective fluorinating capacity.

For customers purchasing DAST for pharmaceutical synthesis, this means that supplier qualification should include more than an assay value.

Important quality considerations include:

Chemical Purity

The concentration of the target DAST should meet the agreed specification.

Water Content

Moisture control is particularly important for this reagent.

Impurity Profile

Potential impurities may affect sensitive fluorination reactions.

Packaging Integrity

The container must provide suitable protection from moisture during storage and transportation.

Batch Consistency

Consistent reagent quality is important when a laboratory reaction is transferred to repeated process manufacturing.

13. What Should Buyers Check Before Purchasing DAST?

When sourcing Diethylaminosulfur trifluoride CAS 38078-09-0, buyers should confirm:

1. Exact chemical identity

Diethylaminosulfur trifluoride

CAS 38078-09-0

2. Molecular specification

C₄H₁₀F₃NS

MW 161.19 g/mol

3. Purity

Confirm the supplier’s assay specification and analytical method.

4. Moisture specification

This is particularly relevant because DAST is moisture sensitive.

5. Packaging

Confirm that the packaging provides appropriate protection during transportation and storage.

6. Storage requirements

Confirm refrigeration and inert-gas requirements where applicable.

7. Documentation

Request:

• · COA
• · SDS
• · Specification sheet
• · Batch information
• · Analytical data
• · Packaging information

For pharmaceutical and API-related applications, these documents can become an important part of supplier qualification.

14. Why Supplier Consistency Matters for DAST

When a reagent is highly reactive, small differences in quality can have an outsized impact on downstream synthesis.

A DAST supplier should therefore be evaluated not only on price but also on:

Manufacturing Control

Consistent production helps maintain predictable reagent performance.

Analytical Capability

Appropriate testing helps identify changes in purity and impurity profile.

Packaging and Storage

Moisture-sensitive reagents require more stringent handling than ordinary organic chemicals.

Supply Reliability

Pharmaceutical development programs may require repeated batches over extended periods.

Technical Support

Clear communication regarding storage, specification, documentation, and logistics can reduce qualification time for international customers.

15. SHLZ Pharma as a DAST Supplier

SHLZ Pharma supplies Diethylaminosulfur trifluoride CAS No. 38078-09-0 as part of its pharmaceutical intermediate and specialty chemical portfolio.

The company’s published information identifies DAST as a nucleophilic fluorinating reagent and provides product information including its molecular formula, molecular weight, density, storage conditions, and moisture sensitivity.

For customers using DAST in pharmaceutical or specialty chemical synthesis, SHLZ Pharma can support procurement requirements involving:

• · Product identification
• · Specification confirmation
• · Batch documentation
• · Packaging requirements
• · Storage information
• · International chemical supply

The objective is to provide customers with a reliable source of a technically demanding fluorination reagent rather than simply offering a catalog chemical.

16. Frequently Asked Questions

What is Diethylaminosulfur trifluoride?

Diethylaminosulfur trifluoride, commonly called DAST, is a nucleophilic fluorinating reagent used in organic synthesis.

What is the CAS number of DAST?

The CAS number is 38078-09-0. PubChem and other chemical databases identify this CAS number for Diethylaminosulfur trifluoride.

What is the molecular formula of DAST?

The molecular formula is C₄H₁₀F₃NS, and its molecular weight is 161.19 g/mol.

What is DAST used for?

DAST is primarily used as a fluorinating reagent, particularly for converting alcohols into alkyl fluorides and aldehydes or ketones into geminal difluorides.

Can DAST be used in pharmaceutical intermediate synthesis?

Yes. DAST has been used in the synthesis of various fluorinated pharmaceutical and medicinal-chemistry intermediates, including reported applications involving 5,5-difluoropipecolic acid and fluorinated carbazole-piperazine derivatives.

Is DAST associated with Belzutifan synthesis?

Yes. Published synthetic studies have reported DAST-mediated fluorination in routes toward fluorinated intermediates associated with Belzutifan. However, this should not be interpreted as meaning that DAST is necessarily the fluorinating reagent used in the current commercial manufacturing process. Later Merck process-development work describes alternative fluorination chemistry for scalable manufacture.

Is DAST moisture sensitive?

Yes. DAST reacts with moisture and water, so it requires appropriate dry storage and handling.

How should DAST be stored?

Supplier information recommends refrigerated, dry storage with protection from moisture; SHLZ Pharma specifies 2–8°C under nitrogen protection for its product information. Customers should always follow the latest SDS and product-specific storage instructions.

Conclusion

Diethylaminosulfur trifluoride (DAST), CAS No. 38078-09-0, is an established and versatile nucleophilic fluorinating reagent used throughout organic synthesis and pharmaceutical chemistry.

With the molecular formula C₄H₁₀F₃NS and molecular weight 161.19 g/mol, DAST provides a practical route for introducing fluorine into appropriately functionalized organic molecules. Its established transformations include the conversion of alcohols to alkyl fluorides and aldehydes or ketones to geminal difluorides.

Its broader synthetic relevance is demonstrated by applications involving 5,5-difluoropipecolic acid, fluorinated carbazole-piperazine derivatives, complex natural-product intermediates, and fluorinated intermediates associated with Belzutifan.

For Belzutifan in particular, published synthetic work demonstrates the use of DAST in fluorination chemistry, while subsequent commercial process-development studies illustrate why reagent selection can change as a synthesis moves from laboratory scale to robust manufacturing.

At the same time, DAST’s high reactivity requires careful attention to moisture control, temperature, packaging, storage, transportation, and process safety. It should be handled only according to appropriate safety documentation and by trained personnel.

For pharmaceutical companies, research organizations, and specialty chemical manufacturers sourcing Diethylaminosulfur trifluoride CAS 38078-09-0, supplier evaluation should therefore consider not only price, but also chemical purity, moisture control, batch consistency, documentation, packaging, and supply reliability.

SHLZ Pharma provides DAST for international customers requiring a reliable fluorinating reagent for pharmaceutical intermediate synthesis, medicinal chemistry, and advanced organic synthesis.