1-Bromo-3-chlorobenzene → (R)-Tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate

HRID 218361Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[CH:3]=1.[Li]CCCC.CCCCCC.CON(C)[C:23]([C@@H:25]1[CH2:30][CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26]1)=[O:24]>C1COCC1>[Cl:8][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[C:23]([C@@H:25]1[CH2:30][CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26]1)=[O:24]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 1-bromo-3-chlorobenzene (54.3 g, 0.286 mol) in anhydrous THF (500 mL) at −78° C. under nitrogen was added drop wise a solution of 2.5 M n-BuLi in hexane (114 mL, 0.286 mol). After stirring for 1 hr at −78° C., a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (65.8 g, 0.242 mol) in anhydrous THF (300 mL) was added drop wise. After addition, the reaction mixture was allowed to warm to room temperature and stirred for 2 h. TLC indicated the reaction was complete. The mixture was quenched with saturated NH4Cl solution (300 mL) and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product (R)-tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate (92 g, 100%), which was used immediately for next step without purification.

Workup

additionAfter addition
temperatureto warm to room temperature
stirringstirred for 2 h
customThe mixture was quenched with saturated NH4Cl solution (300 mL)
extractionextracted with ethyl acetate (3×200 mL)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-897fd6dec5de4c45926d01c412f3ba94
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08198453B2

Reaction notes

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