Sodium Hydroxide → (3-{3-[(2,2-Diphenyl-ethyl)-(3,5-bis(trifluoromethyl)-benzyl)-amino]-propoxy}-phenyl)-acetic acid

HRID 881669Notes

Reaction equation

HRID 881669 reaction equation
C[O:2][C:3](=[O:45])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:31][CH:32]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:16][C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([C:27]([F:30])([F:29])[F:28])[CH:18]=2)[CH:6]=1.[OH-].[Na+]>CO>[C:39]1([CH:32]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:31][N:15]([CH2:16][C:17]2[CH:18]=[C:19]([C:27]([F:28])([F:29])[F:30])[CH:20]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:22]=2)[CH2:14][CH2:13][CH2:12][O:11][C:7]2[CH:6]=[C:5]([CH2:4][C:3]([OH:45])=[O:2])[CH:10]=[CH:9][CH:8]=2)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86626714(3-{3-[(2,2-Diphenyl-ethyl)-(3,5-bis(trifluoromethyl)-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester

Product 1

HCID 86626715(3-{3-[(2,2-Diphenyl-ethyl)-(3,5-bis(trifluoromethyl)-benzyl)-amino]-propoxy}-phenyl)-acetic acidYield 79%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (3-{3-[(2,2-Diphenyl-ethyl)-(3,5-bis(trifluoromethyl)-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester (4e). (0.57 g, 0.001 mol) in methanol (7.5 mL) was treated with 2N NaOH (5 mL) and the mixture stirred overnight at ambient temperature. After concentration to dryness, the residue was dissolved in EtOAc (25 mL) and water was added (10 mL), the solution acidified to pH 3 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, which was purified by flash chromatography (9:1 CH2Cl2/MeOH) to give the desired product as oil 0.49 g in 79% yield. 1H NMR (CD3OD) δ 7.70 (s, 1H), 7.66 (s, 2H), 7.23 (m, 8H), 7.14 (m, 3H), 6.82 (d, 1H), 6.58 (s, 1H), 6.54 (dd, 1H), 4.26 (t, 1H), 3.77 (s, 2H), 3.56 (t, 2H), 3.52 (s, 2H), 3.16 (d, 2H), 2.64 (t, 2H), 1.82 (t, 2H); 13C NMR (CD3OD) δ 175.6, 160.3, 145.3, 144.9, 137.3, 132.4, 130.3, 130.2, 129.4, 129.3, 127.4, 122.5, 121.5, 116.4, 113.9, 66.3, 61.0, 59.1, 51.8, 51.3, 42.1, 27.9. Anal. Calcd for C34H31F6NO3: C, 66.34; H, 5.08; N, 2.08; F, 18.52. Found: C, 66.10; H, 5.07; N, 2.21; F, 18.69.

Workup

  1. concentrationAfter concentration to dryness
  2. dissolutionthe residue was dissolved in EtOAc (25 mL)
  3. additionwater was added (10 mL)
  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-6fc84f5e3a1f490bab86db4221b7349b
Source dataset
uspto-grants-2015_03
Patent number
US08993628B2

Reaction notes

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