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 507044Notes

Reaction equation

HRID 507044 reaction equation
[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]

Participants

5

Reactant 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

Product 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 esterYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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%)

Sources & evidence

ORD record
ord-b3c5d31a46d14241a7be5ca803d59cee
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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