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

HRID 507042Notes

Reaction equation

HRID 507042 reaction equation
Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[F:7][C:8]([F:44])([F:43])[C:9]1[CH:10]=[C:11]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:12][N:13]([C:30]1[N:31]=[N:32][N:33]([CH3:35])[N:34]=1)[C@H:14]1[CH2:20][CH2:19][CH2:18][NH:17][C:16]2[CH:21]=[C:22]([C:26]([F:29])([F:28])[F:27])[C:23]([CH3:25])=[CH:24][C:15]1=2.N1C=CC=CC=1>ClCCl.C(OCC)(=O)C>[CH2:5]([O:4][C:2]([N:17]1[CH2:18][CH2:19][CH2:20][C@H:14]([N:13]([CH2:12][C:11]2[CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=[C:9]([C:8]([F:7])([F:44])[F:43])[CH:10]=2)[C:30]2[N:31]=[N:32][N:33]([CH3:35])[N:34]=2)[C:15]2[CH:24]=[C:23]([CH3:25])[C:22]([C:26]([F:28])([F:27])[F:29])=[CH:21][C:16]1=2)=[O:3])[CH3:6]

Participants

6

Reactant 3

HCID 1049PyridineHCID 10928Ethyl chloroformateHCID 59432408(S)-(3,5-bistrifluoromethylbenzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)amine

Product 1

HCID 11578151(S)-5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid ethyl esterYield 65.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add ethyl chloroformate (0.0223 mL, 0.233 mmol) dropwise to a solution of (S)-(3,5-bistrifluoromethylbenzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)amine (0.0430 g, 0.0778 mmol) (Example 3, Step 18) and pyridine (0.0190 mL, 0.233 mmol) in dichloromethane (1 mL) at room temperature under an atmosphere of nitrogen and stir for 2 h. Dilute the reaction mixture with ethyl acetate (10 mL) and wash with 1.0 N hydrochloric acid (10 mL) and water (3×10 mL). Dry the organic layer over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure. Purify the residue using column chromatography on silica gel, eluting with ethyl acetate/hexanes (0-20%), to provide the title compound (0.0320 g, 65%). MS (ES+): 625 (M+H).

Workup

  1. washwash with 1.0 N hydrochloric acid (10 mL) and water (3×10 mL)
  2. dry with materialDry the organic layer over anhydrous sodium sulfate
  3. filtrationfilter
  4. customremove the solvent under reduced pressure
  5. customPurify the residue
  6. washeluting with ethyl acetate/hexanes (0-20%)

Sources & evidence

ORD record
ord-3da681e2332a47f690693fdca34d7f48
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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