2-Chloro-N-methoxy-N-methylnicotinamide → 3-Acetyl-2-chloropyridine

Temperature

0 °C

A solution of 2-chloro-N-methoxy-N-methyl-nicotinamide (23.6 g, 118 mmol) in tetrahydrofuran (350 mL, 0.34M) at 0° C. was treated dropwise via an addition funnel with methyl magnesium chloride (3.0M solution in tetrahydrofuran, 100 mL, 300 mmol). The reaction became a very thick opaque white mixture and was diluted with additional tetrahydrofuran (150 mL). The reaction was stirred at 0° C. for 1 h. At this time, the reaction was carefully quenched with water (250 mL) and then partitioned between additional water (250 mL) and ethyl acetate (250 mL). The aqueous layer was back extracted with ethyl acetate (2×250 mL). The combined organics were washed with a saturated aqueous sodium chloride solution (250 mL), dried over magnesium sulfate, filtered, rinsed with ethyl acetate, and concentrated in vacuo. Flash chromatography (AnaLogix Intelliflash 280, 400 g silica gel column, 25-50% ethyl acetate/hexanes) afforded 1-(2-chloro-pyridin-3-yl)-ethanone (13.17 g, 72%) as a yellow oil.

1. customAt this time, the reaction was carefully quenched with water (250 mL)
2. custompartitioned between additional water (250 mL) and ethyl acetate (250 mL)
3. extractionThe aqueous layer was back extracted with ethyl acetate (2×250 mL)
4. washThe combined organics were washed with a saturated aqueous sodium chloride solution (250 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. washrinsed with ethyl acetate
8. concentrationconcentrated in vacuo

ORD record

ord-023ee5a9cfa8449394ea2afdde5074d8

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08471027B2