202289-38-1

Usage

Uses

Used in Organic Synthesis:
Bis(2-methoxyethyl)aminosulfur trifluoride is used as a reactant for various fluorination reactions, including the preparation of fluorinated catechols via Umpolung based nucleophilic deoxyfluorination, the synthesis of imidazole derivatives as CXCR3 antagonists, ring expansion reactions, and the conversion of carboxylic acids to aldehydes or ketones through Grignard reagents via in situ generation of Weinreb amides.
Used in Pharmaceutical Industry:
Bis(2-methoxyethyl)aminosulfur trifluoride is used as a key intermediate in the synthesis of pharmaceutical compounds, particularly for the preparation of fluorinated molecules with potential therapeutic applications.
Used in Chemical Research:
Bis(2-methoxyethyl)aminosulfur trifluoride is used as a valuable tool in chemical research for studying the reactivity and selectivity of nucleophilic fluorination reactions, as well as for the development of new synthetic methodologies and applications.

InChI:InChI=1/C6H14F3NO2S/c1-11-5-3-10(4-6-12-2)13(7,8)9/h3-6H2,1-2H3

Synthetic route

N-trimethylsilyl bis(2-methoxyethyl)amine (221557-49-9) → (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1)

Conditions	Yield
With sulfur tetrafluoride In diethyl ether at -30℃;	70%
In diethyl ether at -30 - 0℃; for 3h; Substitution;	2.6 g

Bis-(2-methoxyethyl)amine (111-95-5) → (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: n-BuLi / hexane / -78 - 0 °C 1.2: hexane / 0.5 h / 0 °C 2.1: 2.6 g / diethyl ether / 3 h / -30 - 0 °C View Scheme

2-thiophenylcarboxylic acid (527-72-0) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → thiophene-2-carboxylic acid bis(2-methoxyethyl)amide

Conditions	Yield
Stage #1: 2-thiophenylcarboxylic acid; (bis-(2-methoxyethyl)amino)sulfur trufluoride With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; Stage #2: With diisopropylamine In dichloromethane at 20℃; for 22h;	89%

Benzoylformic acid (611-73-4) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → N,N-bis(2-methoxyethyl)-2-oxo-2-phenylacetamide + 2,2-difluoro-N,N-bis-(2-methoxy-ethyl)-2-phenyl-acetamide

Conditions	Yield
In dichloromethane at 25℃; for 1h;	A 87% B n/a
In dichloromethane at 25℃; for 36h;	A n/a B 84%

methyl 4-(((N-(3-chlorophenyl)-1-(3-hydroxycyclobutyl)piperidine)-4-sulfonamido)methyl)benzoate + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → methyl 4-(((N-(3-chlorophenyl)-1-(3-fluorocyclobutyl)piperidine)-4-sulfonamido)methyl)benzoate

Conditions	Yield
With triethylamine In dichloromethane for 18h; Reflux;	81.2%

(±)-tert-butyl 4-oxo-2-phenylpiperidine-1-carboxylate (849928-30-9) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → tert-butyl 4,4-difluoro-2-phenylpiperidine-1-carboxylate (1257300-29-0)

Conditions	Yield
In dichloromethane at 0 - 20℃;	81%

(bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → bis(2-methoxyethyl)aminodifluorosulfinium tetrafluoroborate

Conditions	Yield
With boron trifluoride diethyl etherate In diethyl ether at 5 - 20℃; Inert atmosphere;	78%

boron trifluoride diethyl etherate (109-63-7) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → bis(2-methoxyethyl)aminodifluorosulfinium tetrafluoroborate

Conditions	Yield
In diethyl ether at 5℃; for 2h; Inert atmosphere; Cooling with ice bath;	78%

1-oxoindane-2-carboxylic acid ethyl ester (6742-25-2) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → C18H25F2NO5S

Conditions	Yield
In tetrahydrofuran at 20℃;	78%

(bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) + phenylboronic acid (98-80-6) → C12H19NO3S

Conditions	Yield
In dichloromethane at 20℃; for 0.0833333h; Schlenk technique;	74%

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → 2-difluoromethylisonicotinic acid ethyl ester (1192539-75-5)

Conditions	Yield
In dichloromethane at 0 - 20℃; for 5h;	73.8%

methyl-6-(((N-(3-chlorophenyl)-1-(3-hydroxycyclobutyl)piperidine)-4-sulfonamido)methyl)nicotinate + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → C23H27ClFN3O4S

Conditions	Yield
In dichloromethane for 18h; Reflux;	72.1%

5-cyano-2-formyl-1H-indole-1-carboxylic acid tert-butyl ester (1401726-77-9) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → 5-cyano-2-difluoromethyl-1H-indole-1-carboxylic acid tert-butyl ester (1401726-78-0)

Conditions	Yield
In dichloromethane at 0 - 25℃; Inert atmosphere;	72%

ethyl 4-(3-bromobenzoyl)-5-formyl-3-methyl-1H-pyrrole-2-carboxylate + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → ethyl 4-(3-bromobenzoyl)-5-(difluoromethyl)-3-methyl-1H-pyrrole-2-carboxylate

Conditions	Yield
In dichloromethane for 8h; Inert atmosphere;	68.1%

benzoic acid (65-85-0) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → N,N-bis(2-methoxyethyl)benzamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 8h;	67%

di-tert-butyl dicarbonate (24424-99-5) + 5-azido-2-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-ol + sodium hydrogencarbonate (144-55-8) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → tert-butyl N-(5-fluoro-2-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-yl)carbamate

Conditions	Yield
With triphenylphosphine In tetrahydrofuran; water	66%

1,1-DIFLUORO-(trans-4-PROPYLCYCLOHEXYL)-1H-NAPHTHALENE-2-ONE + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → 1,1,2,2-tetrafluoro-6-(trans-4-propylcyclohexyl)-1,2-dihydronaphthalene (319906-32-6)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran; methanol	65%
With sodium hydrogencarbonate In tetrahydrofuran; methanol	65%
With sodium hydrogencarbonate In tetrahydrofuran; methanol	65%
With sodium hydrogencarbonate In tetrahydrofuran; methanol	65%

ethyl 2-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxylate (1447943-17-0) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → ethyl 2-(fluoromethyl)tetrahydro-2H-pyran-2-carboxylate (1447943-18-1)

Conditions	Yield
In ethyl acetate at 0 - 70℃;	63%

5-nitroisatin (611-09-6) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → 3,3-difluoro-5-nitro-2,3-dihydroindol-2-one (197067-34-8)

Conditions	Yield
In dichloromethane at 20℃; for 12h;	62.8%
In dichloromethane at 25℃; for 12h;	62.8%

bis(gem-diol) 1,1,1,5,5,5-hexafluoropentane-2,2,4,4-tetraol (428-75-1) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → 1,1,1,5,5,5-hexafluoro-4-bis(2-methoxyethyl)amino-pent-3-en-2-one

Conditions	Yield
In dichloromethane at 20℃; for 4h;	60%

di-tert-butyl dicarbonate (24424-99-5) + 4-azido-7-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-3-one + sodium hydrogencarbonate (144-55-8) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → tert-butyl N-[3,3-difluoro-7-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-yl]carbamate

Conditions	Yield
With triphenylphosphine In tetrahydrofuran; water	59%

4-hydroxymethyl-5H-furan-2-one (80904-75-2) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → 4-fluoromethyl-5H-furan-2-one (916069-77-7)

Conditions	Yield
In ethanol; dichloromethane; water at -10 - 20℃; for 2.83333h;	58%

benzyl 4-azido-5-oxoazepane-1-carboxylate (1338718-19-6) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → benzyl 5-azido-4,4-difluoroazepane-1-carboxylate (1338718-21-0)

Conditions	Yield
In tetrahydrofuran; dichloromethane at 20℃; for 18h;	56%

ethyl (S)-3-hydroxy-2-[(Z)-octadec-9-enamido]propanoate + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → ethyl (S)-(Z)-heptadec-8-en-yl-4,5-dihydrooxazole-4-carboxylate

Conditions	Yield
Stage #1: ethyl (S)-3-hydroxy-2-[(Z)-octadec-9-enamido]propanoate With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.5h; Inert atmosphere; Stage #2: (bis-(2-methoxyethyl)amino)sulfur trufluoride In dichloromethane at 0 - 20℃; for 16h;	56%

tert-butyl 4-(3-chlorophenyl)-3-oxopiperidine-1-carboxylate + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → tert-butyl 4-(3-(ethoxycarbonyl)phenyl)-3,3-difluoropiperidine-1-carboxylate

Conditions	Yield
In dichloromethane at 0 - 20℃; for 1.33333h;	55.3%

(bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) + 3-(4-bromophenyl)cyclobutanone (254892-91-6) → 1-bromo-4-(3,3-difluorocyclobutyl)benzene (1236357-60-0)

Conditions	Yield
Stage #1: (bis-(2-methoxyethyl)amino)sulfur trufluoride; 3-(4-bromophenyl)cyclobutanone With boron trifluoride diethyl etherate In dichloromethane; toluene at 0 - 20℃; Stage #2: With sodium hydroxide In dichloromethane; water; toluene for 0.5h;	54%

1-(6-bromopyridin-3-yl)ethanone (139042-59-4) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → 2-bromo-5-(1,1-difluoroethyl)pyridine

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate for 168h; Inert atmosphere; Molecular sieve;	54%

(bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) + 6-chloroimidazo[1,2-b]pyridazine-3-carbaldehyde → 6-chloro-3-(difluoromethyl)imidazo[1,2-b]pyridazine

Conditions	Yield
In ethanol; dichloromethane at 20℃;	50%

(7-((3aR,4R,6R,6aR)-6-((1R)-(3,4-difluorophenyl)((tetrahydro-2H-pyran-2-yl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)methanol + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → 7-((3aR,4R,6R,6aR)-6-((1R)-(3,4-difluorophenyl)((tetrahydro-2H-pyran-2-yl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-4-(fluoromethyl)-7H-pyrrolo[2,3-d]pyrimidine

Conditions	Yield
In dichloromethane at -70 - 25℃; for 2h;	50%

(2S,5R)-2,2,2-trichloroethyl 2-(hydroxymethyl)-5-phenylmorpholine-4-carboxylate (1349829-39-5) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → (2S,5R)-2,2,2-trichloroethyl 2-(fluoromethyl)-5-phenylmorpholine-4-carboxylate (1349829-40-8)

Conditions	Yield
Stage #1: (2S,5R)-2,2,2-trichloroethyl 2-(hydroxymethyl)-5-phenylmorpholine-4-carboxylate; (bis-(2-methoxyethyl)amino)sulfur trufluoride In 1,2-dichloro-ethane; toluene at 0 - 20℃; Stage #2: With sodium hydroxide In dichloromethane; water	46%

(3aS,5R,5aS,8aR,8bS)-2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxolo)[4,5-b:4',5'-d]pyran-5-carbaldehyde (70932-48-8) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → (3aS,5R,5aS,8aR,8bS)-5-(difluoromethyl)-2,2,7,7-tetramethyltetrahydro-3aH-bis-[1,3]-dioxolo-[4,5-b:4',5'-d]-pyran (70932-51-3)

Conditions	Yield
In ethanol; dichloromethane at 37℃; for 72h; Sealed tube;	46%

Upstream product

• 111-95-5 Bis-(2-methoxyethyl)amine 
• 221557-49-9 [bis(2-methoxyethyl)amino]trimethylsilane 

Downstream Products

• 693220-89-2 (1S,2S)-4-[3-azido-2-fluoro-1-(3-fluoro-phenyl)-propoxy]-5-fluoro-benzo[b]thiophene 
• 439134-96-0 ethyl [2-methyl-4-(1,1,2,2-tetrafluoro-2-{4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}ethyl)phenoxy]acetate 
• 1207747-91-8 7-Bromo-3-(difluoromethyl)quinoline 
• 1211521-60-6 2-bromo-5-(1,1-difluoroethyl)pyridine 
• 1257300-29-0 tert-butyl 4,4-difluoro-2-phenylpiperidine-1-carboxylate 
• 1236357-60-0 1-bromo-4-(3,3-difluorocyclobutyl)benzene 
• 314050-98-1 2-propyl-4-(4',4,-difluorocyclohexyl)phenol 
• 314051-01-9 2-chloro-4-(4',4,-difluorocyclohexyl)phenol 
• 319906-32-6 1,1,2,2-tetrafluoro-6-(trans-4-propylcyclohexyl)-1,2-dihydronaphthalene 
• 7631-86-9 SiO₂ 

Relevant academic research and scientific papers

Bis(2-methoxyethyl)aminosulfur trifluoride: A new broad-spectrum deoxofluorinating agent with enhanced thermal stability

Bis(2-methoxyethyl)aminosulfur trifluoride, (CH3OCH2CH2)2NSF3 (Deoxo-Fluor reagent), is a new deoxofluorinating agent that is much more thermally stable than DAST (C2H5)2NSF3 and its congeners. It is effective for the conversion of alcohols to alkyl fluorides, aldehydes/ketones to the corresponding gem-difluorides, and carboxylic acids to the trifluoromethyl derivatives with, in some cases, superior performance compared to DAST. The enhanced stability is rationalized on the basis of conformational rigidity imposed by a coordination of the alkoxy groups with the electron-deficient sulfur atom of the trifluoride.

Bis(2-methoxyethyl)aminosulfur trifluoride: A new broad-spectrum deoxofluorinating agent with enhanced thermal stability

Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) is effective for the conversion of alcohols to alkyl fluorides, aldehydes/ketones to the corresponding gem-difluorides and also for the transformation of carboxylic acids to their trifluoromethyl derivatives; it is a less thermally sensitive, broader-spectrum alternative to the traditional dialkylaminosulfur trifluoride (DAST) deoxofluorination reagents.