Dimethyl Sulfoxide → (S)-tert-butyl 3-(3-chloro-5-(trifluoromethyl)pyridin-2-ylamino)-2-oxo-1,4'-bipiperidine-1'-carboxylate

HRID 407969Notes

Reaction equation

Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH2:13][C@H:14]1[CH2:19][CH2:18][CH2:17][N:16]([CH:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]2)[C:15]1=[O:33].C([O-])([O-])=O.[Na+].[Na+].CS(C)=O>O>[Cl:8][C:7]1[C:2]([NH:13][C@H:14]2[CH2:19][CH2:18][CH2:17][N:16]([CH:20]3[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[CH2:24][CH2:25]3)[C:15]2=[O:33])=[N:3][CH:4]=[C:5]([C:9]([F:12])([F:11])[F:10])[CH:6]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A flask was charged with 2,3-dichloro-5-(trifluoromethyl)pyridine (0.2919 mL, 2.093 mmol), (S)-tert-butyl 3-amino-2-oxo-1,4′-bipiperidine-1′-carboxylate (0.415 g, 1.395 mmol), Na2CO3 (0.2958 g, 2.791 mmol), and DMSO (5 mL). The reaction mixture was stirred at 130° C. overnight. Water was added and the reaction mixture was extracted with ethyl acetate. The organic layers were combined, dried, filtered, concentrated. The residue was purified using silica gel column chromatography with 30% ethyl acetate in hexanes to provide (S)-tert-butyl 3-(3-chloro-5-(trifluoromethyl)pyridin-2-ylamino)-2-oxo-1,4′-bipiperidine-1′-carboxylate (0.51 g, 76.63% yield). Mass spectrum (apci) m/z=377.2 (M+H-Boc).

Workup

extractionthe reaction mixture was extracted with ethyl acetate
customdried
filtrationfiltered
concentrationconcentrated
customThe residue was purified

Sources & evidence

ORD record: ord-c4291e26255347c48426edd4fbfab978
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754226B2

Reaction notes

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