Sodium hydride → 3-tert-butoxycarbonyl-7-chloro-6-(thiophen-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670547Notes

Reaction equation

[H-].[Na+].[S:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[SH:8].[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([CH2:28]Cl)=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>CN(C=O)C.[I-].[K+]>[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([CH2:28][S:8][C:4]3[S:3][CH:7]=[CH:6][CH:5]=3)=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]

Participants

Conditions

Temperature: 45 °C

Procedure

Suspend sodium hydride (20 mg, 60% dispersion in mineral oil) in anhydrous DMF (2 mL) and add thiophene-2-thiol (35 mg, 0.38 mmol) at room temperature. After 5 min add 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (150 mg, 0.38 mmol) and catalytic potassium iodide (1 mg) in anhydrous DMF (1 mL) and stir at 45° C. for 13 h. Cool the mixture to room temperature and partition between brine and EtOAc. Dry the organic layer over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 7:3 gradient) to give 3-tert-butoxycarbonyl-7-chloro-6-(thiophen-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (110 mg).

Workup

temperatureCool the mixture to room temperature
custompartition between brine and EtOAc
dry with materialDry the organic layer over Na2SO4
filtrationfilter
concentrationconcentrate in vacuo
customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 7:3 gradient)

Sources & evidence

ORD record: ord-e06239ab55a142d59a6d140e0a7ec016
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07994163B2

Reaction notes

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