Phosphorus oxychloride → tert-Butyl 6-bromo-3',6'-dihydro-2,4'-bipyridine-1'(2'H)-carboxylate

HRID 403198Notes

Reaction equation

[Br:1][C:2]1[N:7]=[C:6]([C:8]2(O)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl.C(=O)([O-])O.[Na+]>N1C=CC=CC=1>[Br:1][C:2]1[N:7]=[C:6]([C:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]=2)[CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of tert-butyl 4-(6-bromopyridin-2-yl)-4-hydroxypiperidine-1-carboxylate (100 mg) in pyridine (2.5 ml) is added, at 0° C. under argon, POCl3 (0.26 ml). The mixture is stirred at 0° C. and then slowly warmed to room temperature. The mixture is stirred at room temperature overnight. The reaction mixture is subsequently admixed with saturated sodium hydrogencarbonate solution and the aqueous phase is removed. After the aqueous phase has been extracted with tert-butyl methyl ether, the combined organic phases are dried over sodium sulphate and concentrated under reduced pressure. The residue is purified by chromatography. This gives tert-butyl 6-bromo-3′,6′-dihydro-2,4′-bipyridine-1′(2′H)-carboxylate (60 mg).

Workup

temperatureslowly warmed to room temperature
stirringThe mixture is stirred at room temperature overnight
customthe aqueous phase is removed
extractionAfter the aqueous phase has been extracted with tert-butyl methyl ether
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-e2d965447b0e49699427a2bb749675df
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748420B2

Reaction notes

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