Sodium Hydroxide → (3-{3-[(2,2-Diphenyl-ethyl)-(2-fluoro-3-trifluoromethyl-benzyl)-amino]-propoxy}-phenyl)-acetic acid

HRID 881665Notes

Reaction equation

HRID 881665 reaction equation
C[O:2][C:3](=[O:42])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:28][CH:29]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[C:18]=2[F:27])[CH:6]=1.[OH-].[Na+]>CO>[C:36]1([CH:29]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:28][N:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:24])([F:25])[F:26])[C:18]=2[F:27])[CH2:14][CH2:13][CH2:12][O:11][C:7]2[CH:6]=[C:5]([CH2:4][C:3]([OH:42])=[O:2])[CH:10]=[CH:9][CH:8]=2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68914106(3-{3-[(2,2-Diphenyl-ethyl)-(2-fluoro-3-trifluoromethyl-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester

Product 1

HCID 10153039(3-{3-[(2,2-Diphenyl-ethyl)-(2-fluoro-3-trifluoromethyl-benzyl)-amino]-propoxy}-phenyl)-acetic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (3-{3-[(2,2-Diphenyl-ethyl)-(2-fluoro-3-trifluoromethyl-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester (4a) (0.84 g, 0.0014 mol) in methanol (7.5 mL) was treated with 2N NaOH (5.0 ml) and the mixture stirred overnight at ambient temperature. After concentration to dryness, the residue was diluted with EtOAc (25 mL), water (10 mL) was added, and the solution acidified to pH 2 with concentrated hydrochloric acid, then extracted into EtOAc (3×20 mL). The combined organic extracts were dried over Na2SO4, and then concentrated in vacuo to provide the carboxylic acid as waxy oil. Solidification of the waxy oil from 9:1 ether/pet ether gave white solid (5a) 0.67 g in 85% yield, mp: 181.4° C. 1H NMR (CD3OD) δ 7.84 (d, 2H), 7.46 (m, 11H), 6.88 (d, 2H), 6.68 (d, 2H), 4.67 (s, 2H), 4.64 (t, 1H), 4.11 (s, 2H), 3.99 (d, 2H), 3.54 (s, 2H), 3.45 (d, 2H), 2.27 (t, 2H); 13C NMR (CD3OD) δ 175.3, 159.5, 141.3, 139.1, 137.6, 131.1, 130.6, 130.5, 128.9, 126.8, 126.7, 123.6, 116.9, 114.0, 66.4, 59.0, 53.9, 52.0, 41.5, 23.5. Anal. Calcd for C33H31F4NO3.2H2O: C, 65.87; H, 5.19; N, 2.33; F, 12.63. Found: C, 65.80; H, 5.34; N, 2.08; F, 12.51.

Workup

  1. concentrationAfter concentration to dryness
  2. additionthe residue was diluted with EtOAc (25 mL), water (10 mL)
  3. additionwas added
  4. extractionextracted into EtOAc (3×20 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4118261f07e245f8940a3127b30406ec
Source dataset
uspto-grants-2015_03
Patent number
US08993628B2

Reaction notes

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