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2-Bromoethanol → (S)-5-{(3,5-Bis-trifluoromethyl-benzyl)-(2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl)-amino}-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester

HRID 507044
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HRID 507044 반응식
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:6][N:7]([C:31]1[N:32]=[N:33][NH:34][N:35]=1)[C@H:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:10]2[CH:22]=[C:23]([C:27]([F:30])([F:29])[F:28])[C:24]([CH3:26])=[CH:25][C:9]1=2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:52][CH2:53][OH:54]>CN(C=O)C>[C:18]([O:17][C:15]([N:11]1[CH2:12][CH2:13][CH2:14][C@H:8]([N:7]([CH2:6][C:5]2[CH:4]=[C:3]([C:2]([F:43])([F:1])[F:44])[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=2)[C:31]2[N:32]=[N:33][N:34]([CH2:52][CH2:53][OH:54])[N:35]=2)[C:9]2[CH:25]=[C:24]([CH3:26])[C:23]([C:27]([F:28])([F:29])[F:30])=[CH:22][C:10]1=2)=[O:16])([CH3:20])([CH3:21])[CH3:19]
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참가 물질

5

반응물 3

HCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 59432487(S)-tert-Butyl 5-[(3,5-bistrifluoromethylbenzyl)-(2H-tetrazol-5-yl)amino)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

생성물 1

HCID 59432357(S)-5-{(3,5-Bis-trifluoromethyl-benzyl)-(2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl)-amino}-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester수율 26%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Dissolve (S)-tert-Butyl 5-[(3,5-bistrifluoromethylbenzyl)-(2H-tetrazol-5-yl)amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (Example 3, Step 16) (0.252 g, 0.395 mmole) in DMF (4 mL), add potassium carbonate (0.0929 g, 0.672 mmole) in one portion. Inject 2-bromoethanol (0.0420 mL, 0.593 mmole) dropwise. Stir at room temperature overnight. Partition the reaction mixture between ethyl acetate (50 mL) and water (50 mL). Extract aqueous back with more ethyl acetate (20 mL). Combine organic layers, Dry over sodium sulfate, filter and concentrate the solution. Chromatograph the residue over silica gel, eluting with ethyl acetate/hexanes (0-100%), to provide the title compound as a colorless oil (0.0700 g, 26%). MS (ES+): 705 (M+Na).

후처리

  1. customPartition the reaction mixture between ethyl acetate (50 mL) and water (50 mL)
  2. dry with materialCombine organic layers, Dry over sodium sulfate
  3. filtrationfilter
  4. concentrationconcentrate the solution
  5. washChromatograph the residue over silica gel, eluting with ethyl acetate/hexanes (0-100%)

출처 및 근거

ORD 기록
ord-b3c5d31a46d14241a7be5ca803d59cee
출처 데이터셋
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07786108B2

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