Hydrochloric Acid → (S)-4-{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 507108노트

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HRID 507108 반응식
[OH-].[Na+].C[O:4][C:5](=[O:51])[C:6]1[CH:11]=[CH:10][C:9]([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:8][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:9]2[CH:10]=[CH:11][C:6]([C:5]([OH:51])=[O:4])=[CH:7][CH:8]=2)[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

참가 물질

5

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HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 11600101(S)-4-{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

생성물 1

HCID 11636152(S)-4-{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 acid수율 90.3%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
60 °C

실험 절차

Add 5 N sodium hydroxide solution (0.5 mL) to a solution of (S)-4-{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 (62 mg, 90%). mp 95-98° C.; 1H NMR (CDCl3, 300 MHz) δ 1.63-1.71 (m, 2H), 1.99-2.05 (m, 2H), 2.29 (s, 3H), 2.75-2.84 (m, 1H), 2.98-3.10 (m, 1H), 4.15 (s, 3H), 4.31-4.50 (m, 2H), 4.82-5.12 (m, 2H), 5.51-5.60 (m, 1H), 6.95 (s, 1H), 7.31-7.37 (m, 1H), 7.51-7.60 (m, 2H), 7.65-7.70 (m, 2H), 7.78-7.82 (m, 1H), 8.10-8.17 (m, 2H); ESI MS m/z 687 [C31H27F9N6O2+H]+; HPLC 98.1%, tR 17.0 min.

후처리

  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

출처 및 근거

ORD 기록
ord-ff0285fe912d4600bd7db9c7b7808425
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786108B2

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