Trifluoroacetic acid → (1R,3S)-5,7-difluoro-1-{2-[3-(5-methyl-2-m-tolyloxazol-4-ylmethoxy)cyclohexyloxy]ethyl}-1H-indole-2-carboxylic acid

HRID 553564Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[NH:7][C:6]([C:12]([OH:14])=[O:13])=[CH:5]2.[H-].[Na+].C1(C)C=CC(S(O[CH2:27][CH2:28][O:29][C@@H:30]2[CH2:35][CH2:34][CH2:33][C@H:32]([O:36][CH2:37][C:38]3[N:39]=[C:40]([C:44]4[CH:45]=[C:46]([CH3:50])[CH:47]=[CH:48][CH:49]=4)[O:41][C:42]=3[CH3:43])[CH2:31]2)(=O)=O)=CC=1.C(O)(C(F)(F)F)=O>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([CH2:27][CH2:28][O:29][C@@H:30]1[CH2:35][CH2:34][CH2:33][C@H:32]([O:36][CH2:37][C:38]3[N:39]=[C:40]([C:44]4[CH:45]=[C:46]([CH3:50])[CH:47]=[CH:48][CH:49]=4)[O:41][C:42]=3[CH3:43])[CH2:31]1)[C:6]([C:12]([OH:14])=[O:13])=[CH:5]2

Participants

Conditions

Temperature: 65 °C

Procedure

79 mg of 5,7-difluoroindolecarboxylic acid are dissolved in 2 ml of dried DMF, and 34 mg of 60 percent strength sodium hydride suspension are added. After 30 min at room temperature, 100 mg of ((1R,3S)-[3-(5-methyl-2-m-tolyloxazol-4-ylmethoxy)cyclohexyloxy)ethyl toluene-4-sulfonate, dissolved in 2 ml of DMF, are added. The mixture is stirred at 65° C. until the reaction has gone to completion (monitored by LC-MS). 50 μl of TFA are added, the mixture is filtered and the residue is purified by RP-HPLC. This gives 40 mg of (1R,3S)-5,7-difluoro-1-{2-[3-(5-methyl-2-m-tolyloxazol-4-ylmethoxy)cyclohexyloxy]ethyl}-1H-indole-2-carboxylic acid as a colorless oil. C29H30F2N2O5 (524.56), MS (ESI): 525 (M+H+).

Workup

additionare added
filtrationthe mixture is filtered
customthe residue is purified by RP-HPLC

Sources & evidence

ORD record: ord-34a8230322d246a690e91bcbaed01f3d
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08048901B2

Reaction notes

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