4-Bromo-2-chloro-1-fluorobenzene → HCID 58017422, compound

A solution of 4-bromo-2-chloro-1-fluoro-benzene (31.3 g, 0.15 mol) in anhydrous THF (150 mL) was added dropwise to Mg (4.8 g, 0.2 mol) in THF (50 mL) at rt under nitrogen. The mixture was stirred at 50-60° C. for 1 hr at which time most of the magnesium was consumed. The resulting Grignard reagent was used for the next step. The Grignard reagent was added dropwise to a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (27.2 g, 0.1 mol) in anhydrous THF (300 mL) at −78° C. under nitrogen. After addition, the mixture was allowed to stir at rt for 1.5 hr. The mixture was quenched with saturated NH4Cl solution (300 mL) and extracted with EtOAc (3×200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give crude (R)-tert-butyl 3-(3-chloro-4-fluorobenzoyl)piperidine-1-carboxylate (31.5 g, 92%), which was used immediately for next step without purification.

1. customwas consumed
2. additionAfter addition
3. customThe mixture was quenched with saturated NH4Cl solution (300 mL)
4. extractionextracted with EtOAc (3×200 mL)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo

ORD record

ord-6a1f77ba2b4d42d6b1918dd90df5630e

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08487108B2