Hydrochloric Acid → (S)-5-{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}-nicotinic acid hydrochloride

HRID 507150Notes

Reaction equation

HRID 507150 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:51])[C:6]1[CH:11]=[C:10]([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:9]=[N:8][CH:7]=1.[ClH:52]>CO>[ClH:52].[F:41][C:38]([F:39])([F:40])[C:30]1[CH:29]=[C:28]([CH:33]=[C:32]([C:34]([F:35])([F:36])[F:37])[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:10]2[CH:9]=[N:8][CH:7]=[C:6]([CH:11]=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 59432517(S)-5-{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}-nicotinic acid methyl ester

Product 1

HCID 86615663(S)-5-{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}-nicotinic acid hydrochlorideYield 78%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Add 2 N sodium hydroxide solution (2 mL) to a solution of (S)-5-{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}-nicotinic acid methyl ester (0.090 g, 0.128 mmol) in methanol (5 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 (0.076 g, 78%). 1H NMR (CDCl3, 300 MHz) δ 1.23-2.34 (m, 1H), 1.57-1.64 (m, 2H), 2.03-2.13 (m, 2H), 2.32 (s, 3H), 2.67-2.73 (m, 1H), 3.04-3.14 (m, 1H), 4.14 (s, 3H), 4.32-4.56 (m, 2H), 4.89-5.10 (m, 2H), 5.67-5.70 (m, 1H), 6.89 (s, 1H), 7.23-7.30 (m, 1H), 7.60-7.70 (m, 3H), 8.45 (s, 1H), 8.89 (s, 1H), 9.22 (s, 1H); ESI MS m/z 688 [C30H26F9N7O2+H]+.

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-130b80b7238e4c7f929ce6691fea4095
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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