Lithium hydroxide, monohydrate → 2-(Morpholine-4-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-indole-5-carboxylic acid

HRID 2241530Notes

Reaction equation

HRID 2241530 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][C:16]([F:19])([F:18])[F:17])[C:10]([C:20]([N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)=[O:21])=[CH:9]2)=[O:5])C.O.[OH-].[Li+]>O1CCCC1.CO.O>[N:22]1([C:20]([C:10]2[N:11]([CH2:15][C:16]([F:19])([F:17])[F:18])[C:12]3[C:8]([CH:9]=2)=[CH:7][C:6]([C:4]([OH:5])=[O:3])=[CH:14][CH:13]=3)=[O:21])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68681541HCID 68681541, compound

Product 1

HCID 686815812-(Morpholine-4-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-indole-5-carboxylic acidYield 85%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(morpholine-4-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-indole-5-carboxylic acid ethyl ester (924 mg, 2.4 mmol) and lithium hydroxide monohydrate (200 mg, 4.8 mmol) in tetrahydrofuran (8 mL), methanol (2 mL) and water (4 mL) was refluxed for 3 h. The volatiles were removed in vacuo and the residue was dissolved in water and acidified with hydrochloric acid (1N). The precipitate was filtered, washed with water and dried in vacuo. The crude product was purified by flash chromatography on silica gel with dichloromethane: methanol (98:2 then 19:1 v/v) as eluant, to give 727 mg (85%) of the desired compound as an off-white solid.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe residue was dissolved in water
  3. filtrationThe precipitate was filtered
  4. washwashed with water
  5. customdried in vacuo
  6. customThe crude product was purified by flash chromatography on silica gel with dichloromethane: methanol (98:2

Sources & evidence

ORD record
ord-473f05b86a0d49f0a8026fd2c8b371ba
Source dataset
uspto-grants-2010_05
Patent number
US07723325B2

Reaction notes

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