2,6-Dibromopyridine → tert-Butyl 4-(6-bromopyridin-2-yl)-4-hydroxypiperidine-1-carboxylate

HRID 1910977Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.C([Li])CCC.[O:14]=[C:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.[Cl-].[NH4+]>ClCCl>[Br:8][C:4]1[N:3]=[C:2]([C:15]2([OH:14])[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:19][CH2:20]2)[CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2,6-dibromopyridine (34 g) in dichloromethane (740 ml) is added dropwise, at −78° C. under argon, n-butyllithium (1.6 M in tetrahydrofuran, 100 ml). The reaction mixture is stirred at −78° C. for 20 minutes and then tert-butyl 4-oxopiperidine-1-carboxylate is added. The mixture is stirred at room temperature for 20 minutes. The reaction mixture is subsequently admixed with saturated ammonium chloride solution at −30° C. and the aqueous phase is removed. After the aqueous phase has been extracted with dichloromethane, the combined organic phases are dried over sodium sulphate and concentrated under reduced pressure. The residue is purified by chromatography. This gives tert-butyl 4-(6-bromopyridin-2-yl)-4-hydroxypiperidine-1-carboxylate (60 g).

Workup

stirringThe mixture is stirred at room temperature for 20 minutes
customthe aqueous phase is removed
extractionAfter the aqueous phase has been extracted with dichloromethane
dry with materialthe combined organic phases are dried over sodium sulphate
concentrationconcentrated under reduced pressure
customThe residue is purified by chromatography

Sources & evidence

ORD record: ord-9ff8f1c062bc4788a81a1ff063e3a62d
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08604040B2

Reaction notes

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