Phosgene → 5-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carbonyl chloride

HRID 2353972Notes

Reaction equation

HRID 2353972 reaction equation
[C:1]([Cl:4])(Cl)=[O:2].C(N(C(C)C)CC)(C)C.[F:14][C:15]([F:44])([F:43])[C:16]1[CH:17]=[C:18]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:19][N:20]([CH:24]1[CH2:30][CH2:29][CH2:28][NH:27][C:26]2[CH:31]=[C:32]([Cl:35])[CH:33]=[CH:34][C:25]1=2)[C:21](=[O:23])[CH3:22]>C1(C)C=CC=CC=1>[C:21]([N:20]([CH2:19][C:18]1[CH:36]=[C:37]([C:39]([F:40])([F:41])[F:42])[CH:38]=[C:16]([C:15]([F:14])([F:44])[F:43])[CH:17]=1)[CH:24]1[CH2:30][CH2:29][CH2:28][N:27]([C:1]([Cl:4])=[O:2])[C:26]2[CH:31]=[C:32]([Cl:35])[CH:33]=[CH:34][C:25]1=2)(=[O:23])[CH3:22]

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 59003177N-(3,5-Bis-trifluoromethyl-benzyl)-N-(8-chloro-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-acetamide

Product 1

HCID 866160835-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carbonyl chlorideYield 96%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Add phosgene (1.1 mmol, 1.93 M solution in toluene) followed by diisopropyl ethylamine (1.1 mmol) to a toluene (15 mL) solution of N-(3,5-Bis-trifluoromethyl-benzyl)-N-(8-chloro-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-acetamide (0.50 g, 1.1 mmol) under nitrogen. After stirring at room temperature for 1 h, remove solvent under vacuum. Chromatograph the crude product over silica gel using ethyl acetate/hexane (10-30%) to elute. This provides the title compound (0.55 g, 96%) as an oil which solidifies upon standing: MS (ES+): 527 (M+H).

Workup

  1. customremove solvent under vacuum
  2. washto elute

Sources & evidence

ORD record
ord-14385ef5ef0b4d1980aa601d1f7bcc91
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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