1,2-Dichloroethane → 3-tert-butoxycarbonyl-6-(4-tert-butylcarbamoyl-3-fluorobenzylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911531Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28](O)=[O:29])=[C:24]([F:31])[CH:23]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:32]([NH2:36])([CH3:35])([CH3:34])[CH3:33].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28](=[O:29])[NH:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[C:24]([F:31])[CH:23]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 3-tert-butoxycarbonyl-6-(4-carboxy-3-fluoro-benzylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.1 g, 2.36 mmol) in DMF (7 mL), add tert-butylamine (12.05 g, 165.2 mmol), EDC (1.81 g, 9.44 mmol) and HOBt (1.44 g, 10.62 mmol) and stir in a sealed tube at 70° C. overnight. Dilute with EtOAc, wash with water, dry over anhydrous MgSO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give 3-tert-butoxycarbonyl-6-(4-tert-butylcarbamoyl-3-fluorobenzylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a clear oil. MS (APCI+) m/z: 421 (M+H)+. Use a method similar to the General Procedure 1-4 to give the title compound as a white powder. MS (APCI+) m/z: 421 (M+H)+.

Workup

washwash with water
dry with materialdry over anhydrous MgSO4
concentrationconcentrate in vacuo
customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

Sources & evidence

ORD record: ord-4c187117b7754c0db8576f4f3b644664
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022062B2

Reaction notes

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