4-Fluoro-3-(trifluoromethyl)benzonitrile → 4-[(2R)-2-methylpiperidin-1-yl]-3-(trifluoromethyl)benzonitrile

HRID 2410492Notes

Reaction equation

F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[CH3:14][C@@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][NH:16]1>CS(C)=O.CCOC(C)=O>[CH3:14][C@@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][N:16]1[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-fluoro-3-(trifluoromethyl)benzonitrile (1.0 g, 5.29 mmol) and (R)-(−)-2-methylpiperidine (3.1 mL, 26.4 mmol) was prepared in DMSO (10 mL) and heated at 100° C. under nitrogen for 12 hours. The reaction mixture was diluted with EtOAc, and then washed with water, a saturated aqueous solutions of NaHCO3 and a saturated aqueous solution of NH4Cl. The organic layer was dried (MgSO4) and concentrated under vacuum to give the title compound as a yellow oil, which was used without further purification in the next step. HPLC (Method A) Rt 5.65 min (82.6%). LC/MS (Method B): 269.1 (M+H)+.

Workup

washwashed with water
dry with materialThe organic layer was dried (MgSO4)
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-dc8e3345c06e4775ab2be9e3c05c26c1
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815919B2

Reaction notes

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