Trifluoroacetic acid → (3-Acetyl-5-trifluoromethoxy-indol-1-yl)acetic acid
Reaction equation
C([O:5][C:6](=[O:25])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:14][CH:15]=2)[C:10]([C:22](=[O:24])[CH3:23])=[CH:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[C:22]([C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:20])([F:21])[F:19])[CH:12]=2)[N:8]([CH2:7][C:6]([OH:25])=[O:5])[CH:9]=1)(=[O:24])[CH3:23]Participants
Procedure
To a solution of (3-acetyl-5-trifluoromethoxy-indol-1-yl)-acetic acid tert-butyl ester (680 mg, 1.90 mmol) in CH2Cl2 (10 mL) was added TFA (1.47 mL, 19.0 mmol), and stirring was continued at RT overnight. The reaction mixture was then diluted with CH2Cl2 and MeOH, and volatiles were evaporated under reduced pressure. The residue was taken up in MeOH and then evaporated again. The crude material was taken up in 1M aqueous NaOH solution (5 mL), and the water layer was washed with CH2Cl2 and subsequently acidified to pH=1 by addition of a 6M HCl solution. The precipitate was filtered and dried at 50° C. in vacuo for 1 h to afford the title compound as a off-white solid: MS: 302.0 [M+H]+; tR (HPLC conditions c): 4.40 min. The material thus obtained was used directly in the next step without further purification.
Workup
- customwere evaporated under reduced pressure
- customevaporated again
- washthe water layer was washed with CH2Cl2
- additionsubsequently acidified to pH=1 by addition of a 6M HCl solution
- filtrationThe precipitate was filtered
- customdried at 50° C. in vacuo for 1 h
Sources & evidence
- ORD record
- ord-c12e82a023754fca90ec877ffd1c368f
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09085555B2
Reaction notes
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