Water → (+/-)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 507062Notes

Reaction equation

HRID 507062 reaction equation
[C:1](=O)([O-])[O-].[Na+].[Na+].CI.[F:9][C:10]([F:47])([F:46])[C:11]1[CH:12]=[C:13]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[CH2:14][N:15]([C:34]1[NH:38][N:37]=[N:36][N:35]=1)[CH:16]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[C:18]2[CH:29]=[C:30]([Cl:33])[CH:31]=[CH:32][C:17]1=2.O>CN(C)C=O.CC(C)=O.ClCCl>[F:45][C:42]([F:43])([F:44])[C:40]1[CH:39]=[C:13]([CH:12]=[C:11]([C:10]([F:9])([F:46])[F:47])[CH:41]=1)[CH2:14][N:15]([C:34]1[N:35]=[N:36][N:37]([CH3:1])[N:38]=1)[CH:16]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[C:18]2[CH:29]=[C:30]([Cl:33])[CH:31]=[CH:32][C:17]1=2

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 10340Sodium CarbonateHCID 178459687(+/-)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(1H-tetrazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 11721283(+/-)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 70%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 18184436N,N-dimethylformamide acetoneSolvent

Procedure

Add sodium carbonate (36 mg, 0.34 mmol) and methyl iodide (0.021 mL, 0.34 mmol) to a solution of (+/−)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(1H-tetrazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (98 mg, 0.17 mmol) in dimethylformamide/acetone (1:1) (1 mL). Stir the reaction mixture at room temperature overnight. Then add water and dichloromethane. Separate the layers and wash the organic phase with brine. Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (70 mg, 70%). MS (ES+): 591 (M+H).

Workup

  1. customSeparate the layers
  2. washwash the organic phase with brine
  3. dry with materialDry the organic layer over anhydrous sodium sulfate
  4. filtrationfilter
  5. customremove the solvent under reduced pressure
  6. customPurify the residue by flash chromatography
  7. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-5e47eabe94e149988d5202cb31b6952b
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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