Diketene → (+/-)-5-[(3,5-Bistrifluoromethyl-benzyl)-(3-oxo-butyryl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylic acid isopropyl ester

HRID 507078Notes

Reaction equation

[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:6][NH:7][CH:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[C:10]2[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:9]1=2.[CH2:35]=[C:36]1[O:40][C:38](=[O:39])[CH2:37]1>CN(C)C1C=CN=CC=1.O1CCCC1>[F:34][C:2]([F:1])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:28]=1)[CH2:6][N:7]([C:38](=[O:39])[CH2:37][C:36](=[O:40])[CH3:35])[CH:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[C:10]2[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:9]1=2

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of isopropyl 5-(3,5-bistrifluoromethyl-benzylamino)-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (Example 46, Step 1) (200 mg, 0.39 mmol) and 4-dimethylaminopyridine (6 mg, 0.049 mmol) in dry tetrahydrofuran (1.4 mL) at 0° C. under a nitrogen atmosphere, add a solution of diketene (0.033 mL, 0.43 mmol) in dry tetrahydrofuran (0.4 mL). After stirring 1.5 h at 0° C., remove the solvent under reduced pressure. Purify the by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (169 mg, 73%). MS (ES+): 593 (M+H).

Workup

customremove the solvent under reduced pressure
customPurify the by flash chromatography
washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record: ord-1b9b8dfa6b3b4cf4a78404a87c6397d1
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786108B2

Reaction notes

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