Reaktion #539171

Reaktionsgleichung

(R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

4-bromo-2-chloro-1-fluoro-benzene

magnesium

→

(R)-tert-butyl 3-(3-chloro-4-fluorobenzoyl)piperidine-1-carboxylate

Ausbeute 92.2%

Lösungsmittel

THF

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas consumed
2. 2
   workup.ADDITIONAfter addition
3. 3
   SonstigeThe mixture was quenched with saturated NH4Cl solution (300 mL)
4. 4
   Extraktionextracted with EtOAc (3×200 mL)
5. 5
   WaschenThe combined organic layers were washed with brine
6. 6
   Trocknendried over Na2SO4
7. 7
   Einengenconcentrated in vacuo

Vorschrift

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.

Quelle