Diethyl Carbonate → Ethyl 2-(2-chloropyridin-4-yl)acetate

HRID 2069049Notes

Reaction equation

[Li+].[CH3:2]C([N-]C(C)C)C.[Cl:9][C:10]1(C)[CH:15]=[CH:14][CH:13]=[CH:12][NH:11]1.[CH2:17]([O:19][C:20](=[O:24])OCC)[CH3:18].[NH4+].[Cl-]>C1COCC1>[Cl:9][C:10]1[CH:15]=[C:14]([CH2:2][C:20]([O:19][CH2:17][CH3:18])=[O:24])[CH:13]=[CH:12][N:11]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of LDA (2.0 M in THF, 809 mL, 1.62 mol) was added dropwise over 3 hr to a stirred solution of 2-chloropicoline (43) (59.1 mL, 674 mmol) in THF (500 mL) at −78° C. The reaction mixture was stirred for a further 15 min and then diethylcarbonate (106 mL, 876 mmol) was added in a single portion. After 10 min the reaction mixture was allowed to warm to 0° C., was stirred at this temperature for 20 min and then a saturated aqueous solution of NH4Cl (800 mL) was added. The mixture was extracted with ether and the organic phase was washed with water, dried (MgSO4), and evaporated in vacuo to give a dark oil, (˜200 g) which was purified in three batches by flash column chromatography (SiO2, 330 g, 5-20% EtOAc in isohexane, gradient elution) to give the title compound (44) (72 g, 51%): m/z 200 (M+H)+ (ES+)

Workup

waitAfter 10 min the reaction mixture was allowed
stirringwas stirred at this temperature for 20 min
extractionThe mixture was extracted with ether
washthe organic phase was washed with water
dry with materialdried (MgSO4)
customevaporated in vacuo
customto give a dark oil, (˜200 g) which
customwas purified in three batches by flash column chromatography (SiO2, 330 g, 5-20% EtOAc in isohexane, gradient elution)

Sources & evidence

ORD record: ord-0f61ded08b3d4370850ce6d0314d77c6
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299073B2

Reaction notes

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