Potassium Carbonate → 1-(3-Chloro-5,6,7,8-tetrahydro-4H-thieno[2,3-d]azepin-2-yl)-2,2-dimethyl-propan-1-one

HRID 1019620Notes

Reaction equation

C([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([Cl:24])=[C:16]([C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[S:17][C:11]=2[CH2:10][CH2:9]1)C1C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].ClC(OC(Cl)C)=O>ClC(Cl)C.C(Cl)Cl.CO>[Cl:24][C:15]1[C:12]2[CH2:13][CH2:14][NH:8][CH2:9][CH2:10][C:11]=2[S:17][C:16]=1[C:18](=[O:23])[C:19]([CH3:21])([CH3:20])[CH3:22]

Participants

Conditions

Temperature: 22 °C

Procedure

A solution of the product from step (h) (assumed 0.35 mmol) in anhydrous dichloroethane (2 ml) was cooled to 0° C., treated with K2CO3 (−50 mg) and 1-chloroethyl chloroformate (0.38 ml, 3.5 mmol). The reaction was allowed to warmed to 22° C. for 18 hours. The reaction diluted with CH2Cl2 (50 ml) and washed with sat. NaHCO3 (2×50 ml), brine (50 ml), dried (MgSO4) and solvent evaporated in vacuo providing an oily residue, which was dissolved in anhydrous MeOH (10 ml) and refluxed for 1.5 hours. The MeOH was evaporated in vacuo to give the crude product. A portion of the crude was purified by preparative HPLC-MS to give the title compound. 1H NMR (300 MHz, CDCl3) δ 6.25 (br s, 1H); 3.05-3.19 (m, 8H); 1.34 (s, 9H); MS: ESI (positive): 272, 274 (M+H).

Workup

washwashed with sat. NaHCO3 (2×50 ml), brine (50 ml)
dry with materialdried (MgSO4) and solvent
customevaporated in vacuo
customproviding an oily residue, which
temperaturerefluxed for 1.5 hours
customThe MeOH was evaporated in vacuo
customto give the crude product
customA portion of the crude was purified by preparative HPLC-MS

Sources & evidence

ORD record: ord-9f24bab77b0c4a8dacad2da46856a917
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716276B2

Reaction notes

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