Pyridine → 5-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid cyclopentyl ester

HRID 2353970Notes

Reaction equation

HRID 2353970 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH:5]1([OH:10])[CH2:9][CH2:8][CH2:7][CH2:6]1.C(N(C(C)C)CC)(C)C.[F:20][C:21]([F:50])([F:49])[C:22]1[CH:23]=[C:24]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:25][N:26]([CH:30]1[CH2:36][CH2:35][CH2:34][NH:33][C:32]2[CH:37]=[C:38]([Cl:41])[CH:39]=[CH:40][C:31]1=2)[C:27](=[O:29])[CH3:28].N1C=CC=CC=1>C(Cl)Cl>[CH:5]1([O:10][C:1]([N:33]2[CH2:34][CH2:35][CH2:36][CH:30]([N:26]([C:27](=[O:29])[CH3:28])[CH2:25][C:24]3[CH:42]=[C:43]([C:45]([F:46])([F:47])[F:48])[CH:44]=[C:22]([C:21]([F:20])([F:49])[F:50])[CH:23]=3)[C:31]3[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:32]2=3)=[O:2])[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

7

Reactant 5

HCID 1049PyridineHCID 6371PhosgeneHCID 7298CyclopentanolHCID 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 590031395-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid cyclopentyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Add phosgene (0.5 mmol) to a solution of cyclopentanol (0.5 mmol) in DCM (1 mL) at 0° C. under nitrogen. To this cooled solution add diisopropyl ethylamine (0.5 mmol) dropwise. After stirring for 1 h with cooling, warm the mixture to room temperature and add N-(3,5-Bis-trifluoromethyl-benzyl)-N-(8-chloro-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-acetamide (0.05 g, 0.11 mmol) in dichloromethane (0.5 mL) and pyridine (0.5 mmol). After stirring at room temperature for 14-16 h dilute the reaction with dichloromethane (2 mL) and wash with 5% HCl (2 mL) followed by water (2 mL) and brine (2 mL). Dry the organics over sodium sulfate, filter, and remove solvent under vacuum. Chromatograph the crude mixture over silica gel using ethyl acetate/hexane (10-30%) to elute. This affords the title compound (0.06 g, 95%) as an oil which crystallizes upon standing: MS (ES+): 577 (M+H).

Workup

  1. temperaturewith cooling
  2. stirringAfter stirring at room temperature for 14-16 h
  3. additiondilute
  4. washwash with 5% HCl (2 mL)
  5. dry with materialDry the organics over sodium sulfate
  6. filtrationfilter
  7. customremove solvent under vacuum
  8. washto elute

Sources & evidence

ORD record
ord-f8fbed3a99914a7b89bbac5066933b7d
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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