Hydrochloric Acid → Ethyl 1-(6-chloropyridin-3-yl)cyclopropanecarboxylate

HRID 557855Notes

Reaction equation

[H-].[Na+].[Cl:3][C:4]1[N:9]=[CH:8][C:7]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:6][CH:5]=1.CN(C)C=O.Br[CH2:22][CH2:23]Cl.Cl>CCOC(C)=O>[Cl:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:23][CH2:22]2)=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 35 °C

Procedure

Sodium hydride (60% in mineral oil, 0.60 g, 15 mmol) was added to a solution of ethyl (6-chloropyridin-3-yl)acetate (1.0 g, 0.0050 mol) in N,N-dimethylformamide (10 mL, 0.1 mol) at rt under an atmosphere of nitrogen. After 30 minutes, 1-bromo-2-chloro-ethane (0.84 mL, 0.010 mol) was added to the mixture at 0° C. The reaction mixture was stirred at 35° C. for 4 hours and then at room temperature overnight. The mixture was poured into a mixture of ice-water (50 ml) and EtOAc (50 ml) and the resulting mixture was acidified (to pH 2) by slow addition of 6 N HCl. The layers were separated and the organic layer was washed successively with water and brine, dried over MgSO4 and concentrated. The residue was chromatographed by combiflash (ethyl acetate in hexanes: 80%, on silica gel) to afford the desired product. LC/MS: 226.0 and 228.0 (M+H+).

Workup

customat room temperature
customovernight
customThe layers were separated
washthe organic layer was washed successively with water and brine
dry with materialdried over MgSO4
concentrationconcentrated
customThe residue was chromatographed by combiflash (ethyl acetate in hexanes: 80%, on silica gel)

Sources & evidence

ORD record: ord-b19740d08bea4c748a813dea643e86a6
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08058288B2

Reaction notes

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