Lithium hydroxide, monohydrate → (R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)indol-3-yl-methyl]benzoic acid

HRID 1975434Notes

Reaction equation

HRID 1975434 reaction equation
O.[OH-].[Li+].[CH3:4][O:5][C:6]1[CH:7]=[C:8]([CH:13]=[CH:14][C:15]=1[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:26](=[O:36])[NH:27][CH2:28][C@H:29]([CH3:35])[CH2:30][C:31]([F:34])([F:33])[F:32])[CH:24]=2)[N:19]([CH3:37])[CH:18]=1)[C:9]([O:11]C)=[O:10]>O.CO>[CH3:4][O:5][C:6]1[CH:7]=[C:8]([CH:13]=[CH:14][C:15]=1[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:26](=[O:36])[NH:27][CH2:28][C@H:29]([CH3:35])[CH2:30][C:31]([F:33])([F:32])[F:34])[CH:24]=2)[N:19]([CH3:37])[CH:18]=1)[C:9]([OH:11])=[O:10]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 10050661Benzoic acid, 3-methoxy-4-[[1-methyl-5-[[(4,4,4-trifluoro-2-methylbutyl)amino]carbonyl]-1H-indol-3-yl]methyl]-, methyl ester, (R)-

Product 1

HCID 10389603(R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)indol-3-yl-methyl]benzoic acidYield 102.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of lithium hydroxide monohydrate (7.68 g) in water (50 mL) was added to a stirred solution of methyl (R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)indol-3-ylmethyl]benzoate (14.38 g) in methanol (120 mL) and distilled tetrahydrofuran (120 mL) under an inert atmosphere. After 18 h the solvent was evaporated, the residue was dissolved in water (250 mL) and distilled tetrahydrofuran (23 mL), acidified to pH 1 by addition of concentrated hydrochloric acid, and diluted with water (150 mL). The precipitate was collected and washed with water to give (R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)indol-3-ylmethyl]benzoic acid (14.28 g, 100%); mp 218°-223° C.; partial NMR (300 MHz, DMSO-d6): 1.00 (d, 3H, CH ), 2.04-2.28 (m, 2H, CF3CH2), 2.32-2.44 (m, 1H, CHCH3), 3.21 (br t, 2H, CH2N), 3.76 (s, 3H, NCH3), 3.90 (s, 3H, OCH3), 4.07 (s, 2H, ArCH2Ar'), 8.43 (br t, 1H, NHCO).

Workup

  1. distillationdistilled tetrahydrofuran (120 mL) under an inert atmosphere
  2. customAfter 18 h the solvent was evaporated
  3. dissolutionthe residue was dissolved in water (250 mL)
  4. distillationdistilled tetrahydrofuran (23 mL)
  5. additionacidified to pH 1 by addition of concentrated hydrochloric acid
  6. additiondiluted with water (150 mL)
  7. customThe precipitate was collected
  8. washwashed with water

Sources & evidence

ORD record
ord-057502badd2c4853b92756c02e14fb1a
Source dataset
uspto-grants-1994_02
Patent number
US05286740

Reaction notes

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