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}-2-hydroxy-benzoic acid

HRID 507147ノート

反応式

HRID 507147 の反応式
[OH-].[Na+].C[O:4][C:5](=[O:52])[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]=[CH:8][C:7]=1[OH:51].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:10]2[CH:9]=[CH:8][C:7]([OH:51])=[C:6]([CH:11]=2)[C:5]([OH:52])=[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

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59432500(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}-2-hydroxy-benzoic acid methyl ester

生成物 1

HCID 59432361(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}-2-hydroxy-benzoic acid収率 78%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
60 °C

実験手順

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}-2-hydroxy-benzoic acid methyl ester (0.100 g, 0.139 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 1.23-1.32 (m, 2H), 1.51-1.52 (m, 2H), 1.94-2.05 (m, 1H), 2.25 (s, 3H), 2.65-2.71 (m, 1H), 2.95-3.04 (m, 1H), 4.10-4.21 (m, 5H), 4.76-5.03 (m, 2H), 5.50-5.61 (m, 1H), 6.68-6.89 (m, 2H), 7.31-7.40 (m, 2H), 7.49-7.62 (m, 2H), 7.70 (s, 1H), 7.98 (s, 1H), 10.43 (s, 1H); ESI MS m/z 703 [C31H27F9N6O3+H]+.

後処理

  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

出典と根拠

ORDレコード
ord-a001fe06d9c4450a97f50f450bce4e80
出典データセット
uspto-grants-2010_08
特許番号
US07786108B2

反応ノート

読み込み中…