Acetic Anhydride → HCID 59351377, compound

To an ice cooled solution of 2-chloro-3-(piperidin-4-yl)pyrazine-3TFA (150 g, 0.278 mol) in anhydrous dichloromethane (1.5 L) kept under nitrogen was added triethylamine (194 mL, 1.39 mol, 5 eq.) over a period of 15 min., followed by acetic anhydride (53 mL, 0.556 mol, 2 eq.) over a period of 10 min. The resulting mixture was allowed to stir at room temperature for 2 h and quenched with 500 mL of water. After separation, the organic phase was further washed with water (500 mL) and brine (500 mL). The aqueous phases were combined and back extracted with dichloromethane (1 L). Organic extracts were combined, dried and concentrated. The resulting residue was purified by column chromatography (eluting with hexanes/ethyl acetate=2:3 to 100% ethyl acetate) to give 70 g 1-(4-(3-chloropyrazin-2-yl)piperidin-1-yl)ethanone. Yield: 94% for two steps.

1. customquenched with 500 mL of water
2. customAfter separation
3. washthe organic phase was further washed with water (500 mL) and brine (500 mL)
4. extractionback extracted with dichloromethane (1 L)
5. customdried
6. concentrationconcentrated
7. customThe resulting residue was purified by column chromatography (eluting with hexanes/ethyl acetate=2:3 to 100% ethyl acetate)

ORD record

ord-e1f6abf0e19744939b0ab89bc0c508e2

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952037B2