Dimethylformamide → 3-tert-butoxycarbonyl-7-chloro-6-(1-cyano-cyclopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041610Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22]2[C:25]([S:30][CH2:31][C:32]#[N:33])=[C:26]([Cl:29])[CH:27]=[CH:28][C:21]=2[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].Br[CH2:35][CH2:36]Br.CN(C=O)C>C1(C)C=CC=CC=1>[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22]2[C:25]([S:30][C:31]3([C:32]#[N:33])[CH2:36][CH2:35]3)=[C:26]([Cl:29])[CH:27]=[CH:28][C:21]=2[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

Conditions

Temperature: 38 °C

Procedure

Add sodium bis(trimethylsilyl)amide (5.4 mL, 5.4 mmol, 1M solution in THF) at room temperature under nitrogen to a solution of 3-tert-butoxycarbonyl-7-chloro-6-(1-cyano-methylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (380 mg, 1.1 mmol) in anhydrous toluene (4 mL). Stir the solution for 10 min, then add quickly 1,2-dibromoethane (2.8 mL, 32.4 mmol) followed by anhydrous DMF (4 mL). An exothermic reaction was observed and the reaction temperature increased to 38° C. Stir the mixture for 15 min at ambient temperature, then quench with methanol (2 mL). Concentrate in vacuo and purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to obtain 3-tert-butoxycarbonyl-7-chloro-6-(1-cyano-cyclopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (259 mg).

Workup

customAn exothermic reaction
stirringStir the mixture for 15 min at ambient temperature
customquench with methanol (2 mL)
concentrationConcentrate in vacuo
custompurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

Sources & evidence

ORD record: ord-9267540c20da48ed8f1e1fb1f63e1c25
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580780B2

Reaction notes

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