202289-38-1

Basic information

• Product Name: Bis(2-methoxyethyl)aminosulfur trifluoride
• Synonyms: Bis(2-methoxyethyl)aminosulphur trifluoride (50% solution in THF);DEOXO-FLUOR(R), 50% SOLUTION IN TOLUENE;DEOXO-FLUOR(R), 50% SOLUTION IN THF;(BIS(2-METHOXYETHYL)AMINO)SULFUR &;Bis(2-methoxyethyl)aminosulphurtrifluoride(solutioninTHF);[Bis(2-methoxyethyl)amino]sulfur trifluoride, 50% solution in toluene;bis(2-methoxyethyl)amino-sulfur trifluoride solution;deoxo-fluor solution
• CAS NO: 202289-38-1
• Molecular Formula: C₆H₁₄F₃NO₂S
• Molecular Weight: 221.2410696
• EINECS: 478-190-3
• Product Categories: Fluorinating Reagents;Nucleophilic Fluorinating Reagents;Fluorinating Reagents & Building Blocks for Fluorinated Biochemical Compounds;Synthetic Organic Chemistry
• Mol File: 202289-38-1.mol
• Article Data: 2

Chemical Properties

• Boiling Point: >80°C
• Flash Point: 205 °F
• Appearance: clear yellow/liquid
• Density: 1.2 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0155mmHg at 25°C
• Refractive Index: 1.4270 to 1.4310
• Storage Temp.: 2-8°C
• PKA: -7.46±0.70(Predicted)
• Merck: 14,2897
• CAS DataBase Reference: Bis(2-methoxyethyl)aminosulfur trifluoride(CAS DataBase Reference)
• NIST Chemistry Reference: Bis(2-methoxyethyl)aminosulfur trifluoride(202289-38-1)
• EPA Substance Registry System: Bis(2-methoxyethyl)aminosulfur trifluoride(202289-38-1)

Safety Data

• Hazard Codes: T,C,F
• Statements: 14-23/25-29-35-67-65-63-48/20-25-11-40-37-19
• Safety Statements: 23-26-36/37/39-43-45-8-62-46-25-16
• RIDADR: UN REST
• WGK Germany: 3
• F: 10-21
• HazardClass: KEEP COLD, CORROSIVE
• PackingGroup: Ⅰ
• Hazardous Substances Data: 202289-38-1(Hazardous Substances Data)

Usage

Chemical Properties

Dark yellow-orange liquid

Uses

Different sources of media describe the Uses of 202289-38-1 differently. You can refer to the following data:
1. Versatile, thermally stable nucleophilic fluorinating reagent.
2. Reactant for:Fluorination reactionsPreparation of fluorinated catechols via Umpolung based nucleophilic deoxyfluorinationPreparation of imidazole derivatives as CXCR3 antagonistsRing expansion reactionsSynthesis of acyl azides from carboxylic acidsAldehydes or ketones from carboxylic acids and Grignard reagents via in situ generation of Weinreb amides

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

• 314051-01-9 2-chloro-4-(4',4,-difluorocyclohexyl)phenol 
• 7631-86-9 SiO₂ 
• 1349829-40-8 (2S,5R)-2,2,2-trichloroethyl 2-(fluoromethyl)-5-phenylmorpholine-4-carboxylate 
• 1338718-21-0 benzyl 5-azido-4,4-difluoroazepane-1-carboxylate 
• 1268511-91-6 2-bromo-1-(cyclopropylmethoxy)-4-(difluoromethyl)benzene 
• 1257300-29-0 tert-butyl 4,4-difluoro-2-phenylpiperidine-1-carboxylate 
• 1236357-60-0 1-bromo-4-(3,3-difluorocyclobutyl)benzene 
• 1207747-91-8 7-Bromo-3-(difluoromethyl)quinoline 
• 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 
• 314050-98-1 2-propyl-4-(4',4,-difluorocyclohexyl)phenol 
• 319906-32-6 1,1,2,2-tetrafluoro-6-(trans-4-propylcyclohexyl)-1,2-dihydronaphthalene 
• 693220-89-2 (1S,2S)-4-[3-azido-2-fluoro-1-(3-fluoro-phenyl)-propoxy]-5-fluoro-benzo[b]thiophene 

Relevant articles and documents

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.