Hydrochloric Acid → (S)-3-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-benzoic acid

HRID 507110Notes

Reaction equation

HRID 507110 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:51])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][N:13]2[CH2:19][CH2:18][CH2:17][C@H:16]([N:20]([CH2:27][C:28]3[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=3)[C:21]3[N:22]=[N:23][N:24]([CH3:26])[N:25]=3)[C:15]3[CH:42]=[C:43]([CH3:50])[C:44]([C:46]([F:49])([F:48])[F:47])=[CH:45][C:14]2=3)[CH:7]=1.Cl>CO>[F:36][C:34]([F:35])([F:37])[C:32]1[CH:33]=[C:28]([CH:29]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:31]=1)[CH2:27][N:20]([C:21]1[N:22]=[N:23][N:24]([CH3:26])[N:25]=1)[C@H:16]1[CH2:17][CH2:18][CH2:19][N:13]([CH2:12][C:8]2[CH:7]=[C:6]([CH:11]=[CH:10][CH:9]=2)[C:5]([OH:51])=[O:4])[C:14]2[CH:45]=[C:44]([C:46]([F:47])([F:48])[F:49])[C:43]([CH3:50])=[CH:42][C:15]1=2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 11563865(S)-3-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-benzoic acid methyl ester

Product 1

HCID 11571145(S)-3-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-benzoic acidYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Add 5 N sodium hydroxide solution (0.5 mL) to a solution of (S)-3-{5-[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-benzoic acid methyl ester (70 mg, 0.100 mmol) in methanol (1 mL) and heat at 60° C. for 4 h. After the reaction cools to room temperature, acidify to pH 4 with 2 N hydrochloric acid solution and extract the aqueous mixture with ethyl acetate (3×10 mL). Wash the organic layer with water and brine (10 mL each). Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure to provide the title compound as a white solid (67 mg, >99%): mp 83-86° C.; 1H NMR (CDCl3, 300 MHz) δ 1.51-1.71 (m, 2H), 2.00-2.12 (m, 2H), 2.29 (s, 3H), 2.78-2.85 (m, 1H), 3.02-3.09 (m, 1H), 4.17 (s, 3H), 4.31-4.43 (m, 2H), 4.86-5.16 (m, 2H), 5.51-5.60 (m, 1H), 6.98 (s, 1H), 7.25 (s, 1H), 7.43-7.49 (m, 1H), 7.60-7.82 (m, 4H), 7.99-8.03 (m, 1H), 8.15 (s, 1H); ESI MS m/z 687 [C31H27F9N6O2+H]+; HPLC 97.6%, tR 17.0 min.

Workup

  1. customcools to room temperature
  2. extractionextract the aqueous mixture with ethyl acetate (3×10 mL)
  3. washWash the organic layer with water and brine (10 mL each)
  4. dry with materialDry the organic layer over anhydrous sodium sulfate
  5. filtrationfilter
  6. customremove the solvent under reduced pressure

Sources & evidence

ORD record
ord-6ae103404ad54c83a29953713cf643a9
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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