Triethylamine → Methyl 2-(3-fluoro-4-(trifluoromethylsulfonyloxy)phenyl)acetate
Reaction equation
FC(F)(F)S([O:6][S:7]([C:10]([F:13])([F:12])[F:11])(=[O:9])=[O:8])(=O)=O.[F:16][C:17]1[CH:18]=[C:19]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH:20]=[CH:21][C:22]=1O.C(N(CC)CC)C>C(Cl)Cl>[F:16][C:17]1[CH:18]=[C:19]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH:20]=[CH:21][C:22]=1[O:6][S:7]([C:10]([F:11])([F:12])[F:13])(=[O:8])=[O:9]Participants
Conditions
- Temperature
- 0 °C
Procedure
Trifluoromethanesulphonic anhydride (2.67 mL, 16.29 mmol) was added dropwise to a stirred solution of methyl 2-(3-fluoro-4-hydroxyphenyl)acetate (85% by LCMS) (2 g, 10.86 mmol) in DCM (47.1 mL) cooled to 0° C., over a period of 5 minutes under nitrogen. Triethylamine (4.54 mL, 32.58 mmol) was added dropwise over 5 minutes (keeping internal temperature between 5-10° C.) and the resulting solution stirred at room temperature for 4 hours under nitrogen. The reaction mixture was diluted with DCM (100 mL), and washed sequentially with water (100 mL), saturated NaHCO3 (100 mL), and water (100 mL). The organic layer was dried by passing through a phase seperating cartridge and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-(3-fluoro-4-(trifluoromethylsulfonyloxy)phenyl)acetate (2.250 g, 65.5%) as a straw yellow oil.
Workup
- washwashed sequentially with water (100 mL), saturated NaHCO3 (100 mL), and water (100 mL)
- customThe organic layer was dried
- customseperating cartridge
- customevaporated
- customto afford crude product
- customThe crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane
- customPure fractions were evaporated to dryness
Sources & evidence
- ORD record
- ord-1ccd8f7e1c8f496baefa244f7afbc763
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08188092B2
Reaction notes
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