Dimethyl Carbonate → Methyl (2-chloropyridin-4-yl)acetate

HRID 1869734Notes

Reaction equation

[Li+].CC([N-]C(C)C)C.[Cl:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][N:11]=1.[C:17](=O)([O:20]C)[O:18][CH3:19]>C1COCC1>[CH3:19][O:18][C:17](=[O:20])[CH2:16][C:14]1[CH:13]=[CH:12][N:11]=[C:10]([Cl:9])[CH:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of LDA (1.8M in THF/heptane/ethyl benzene, 223 ml, 401 mmol) was added slowly to a stirred solution of 2-chloro-4-methylpyridine (17.5 ml, 200 mmol) in dry THF (1 L) under N2, such that the internal temperature <−70° C. After 1 hour at this temperature, dimethyl carbonate (40 ml, 475 mmol) was added. After 30 minutes the reaction was transferred to a cold bath at −40° C., and then allowed to warm slowly to 0° C. After 1 hour at 0° C. the reaction was quenched with saturated aqueous NH4Cl (250 ml). The mixture was partitioned between EtOAc/H2O. The aqueous layer was extracted with EtOAc (×2). The combined extracts were washed with brine (×1), then dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica, eluting with 10-25% EtOAc/isohexane to give the ester (27.8 g, 75%) as a pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ: 3.63 (2H, s), 3.73 (3H, s), 7.17 (1H, dd, J 5.1, 1.4), 7.28 (1H, s), 8.34 (1H, d, J 5.1).

Workup

customAfter 1 hour at 0° C. the reaction was quenched with saturated aqueous NH4Cl (250 ml)
customThe mixture was partitioned between EtOAc/H2O
extractionThe aqueous layer was extracted with EtOAc (×2)
washThe combined extracts were washed with brine (×1)
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated
customThe residue was purified by chromatography on silica
washeluting with 10-25% EtOAc/isohexane

Sources & evidence

ORD record: ord-b852a441cdcc425789e3a5fac262d330
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07638629B2

Reaction notes

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