2,3-Dichloro-5-(trifluoromethyl)pyridine → Tert-butyl (1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)carbamate

HRID 2239573Notes

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.[NH:13]1[CH2:18][CH2:17][CH:16]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:15][CH2:14]1.C(=O)([O-])N.[K+]>CN(C=O)C>[C:22]([O:21][C:20](=[O:26])[NH:19][CH:16]1[CH2:17][CH2:18][N:13]([C:2]2[C:7]([Cl:8])=[CH:6][C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=2)[CH2:14][CH2:15]1)([CH3:25])([CH3:23])[CH3:24]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 2,3-dichloro-5-(trifluoromethyl)pyridine (2.0 g, 9.26 mmol), tert-butyl piperidine-4-ylcarbamate (2.2 g, 111.1 mmol) and anhydrous potassium carbamate (3.8 g, 27.78 mmol) in DMF (15 ml) was heated in a microwave reactor at 150° C. for 10 min. The mixture was concentrated, water and EtOAc were added to the residue and the aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated. The crude product was purified by flash column chromatography (hexane/EtOAc 90:10) to yield the title compound (2.5 g, 70%). 1H NMR (500 MHz, CDCl3): δ 1.47 s, 9H), 1.53-1.60 (m, 2H), 2.07-2.09 (m, 2H), 3.01-3.06 (m, 2H), 3.72 (br.s., 1H), 3.97-4.00 (m, 2H, 4.54 (br.s., 1H), 7.75 (s, 1H), 8.38 (s, 1H); Mass Spectrum: M+H+ 380.

Workup

concentrationThe mixture was concentrated
additionwater and EtOAc were added to the residue
extractionthe aqueous phase was extracted with EtOAc
dry with materialThe combined organic phases were dried over Na2SO4
concentrationconcentrated
customThe crude product was purified by flash column chromatography (hexane/EtOAc 90:10)

Sources & evidence

ORD record: ord-7ca600024f3549d0b00f734afb0e8ad1
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723333B2

Reaction notes

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