Tetrabutylammonium Fluoride → 3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoic acid methyl ester

HRID 346845Notes

Reaction equation

[CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11]([O:20][Si](CC)(CC)CC)([C:16]([F:19])([F:18])[F:17])[C:12]([F:15])([F:14])[F:13])[CH:8]=2)[NH:3]1.[CH3:28][O:29][C:30](=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37]Cl)[CH:32]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C.C1COCC1>[CH3:28][O:29][C:30](=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][N:3]2[C:4]3[C:9](=[CH:8][C:7]([C:11]([OH:20])([C:16]([F:17])([F:18])[F:19])[C:12]([F:14])([F:15])[F:13])=[CH:6][CH:5]=3)[CH2:10][CH:2]2[CH3:1])[CH:32]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 94 mg (0.23 mmol) of 2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole in 0.5 mL of DMF were added 104 mg (0.45 mmol) of 3-chloromethyl-benzoic acid methyl ester and the mixture was stirred at 80° C. for 10 hrs. After cooling to RT the mixture was treated with 0.5 mL of a 1M solution of TBAF in THF and stirred for an hour at 60° C. Evaporation of the solvent and chromatography on silica gel with EtOAc/n-heptane gave 58 mg (99%) of 3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoic acid methyl ester, light red oil, MS: 448 (MH+).

Workup

temperatureAfter cooling to RT the mixture
stirringstirred for an hour at 60° C
customEvaporation of the solvent and chromatography on silica gel with EtOAc/n-heptane

Sources & evidence

ORD record: ord-9fb99e726a104719b19eff19b0780924
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07173048B2

Reaction notes

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