Triethylamine → 3,6-difluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine

HRID 1623230Notes

Reaction equation

F[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([F:9])[N:3]=1.[O:10]1[CH2:15][CH2:14][CH:13]([CH2:16][NH2:17])[CH2:12][CH2:11]1.C(N(CC)CC)C>CN1C(=O)CCC1.CCOC(C)=O.[Cl-].[Na+].O.O>[F:8][C:7]1[C:2]([NH:17][CH2:16][CH:13]2[CH2:14][CH2:15][O:10][CH2:11][CH2:12]2)=[N:3][C:4]([F:9])=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 2,3,6-trifluoropyridine (3 g, 22.54 mmol), (tetrahydro-2H-pyran-4-yl)methanamine (3.89 g, 33.8 mmol) and triethylamine (7.86 mL, 56.4 mmol) in NMP (60 mL) was heated at about 70° C. for about 1 hr. The reaction mixture was cooled to ambient temperature, diluted with EtOAc (˜100 mL), brine (˜50 mL) and water (˜50 mL). The separated organic layer was washed with brine (1×), 0.3N aqueous HCl (2×), saturated aqueous NaHCO3 solution (1×), brine (1×), dried over Na2SO4, filtered off and concentrated in vacuo providing crude 3,6-difluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine, which was directly used in the next reaction without further purification. Yield: 3.5 g. LCMS (m/z): 229.1 [M+H]+; Retention time=0.79 min.

Workup

temperatureThe reaction mixture was cooled to ambient temperature
washThe separated organic layer was washed with brine (1×), 0.3N aqueous HCl (2×), saturated aqueous NaHCO3 solution (1×), brine (1×)
dry with materialdried over Na2SO4
filtrationfiltered off
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-2cde24acfb09496eafc74de828301a97
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08778951B2

Reaction notes

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