Water → N-(2,4-dimethoxybenzyl)-5-fluoropyridin-2-amine

HRID 2178124Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].F[C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][N:9]=1.[CH3:15][O:16][C:17]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:18]=1[CH2:19][NH2:20].O>CS(C)=O.C(OCC)(=O)C>[CH3:15][O:16][C:17]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:18]=1[CH2:19][NH:20][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][N:9]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Potassium carbonate (16.75 g, 128.1 mmol) was added to a solution of 2,5-difluoropyridine (4.91 g, 42.7 mmol) and 2,4-dimethoxybenzylamine (6.85 g, 42.7 mmol) in DMSO (30 mL). The mixture was heated to 110° C. for 16 hours, cooled to room temperature and poured into water (100 mL) and ethyl acetate (100 mL). The organic layer was separated and the aqueous layer was extracted with two further portions of ethyl acetate (25 mL). The combined organic extracts were washed with brine (50 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 10 to 30% ethyl acetate in heptanes to afford the title compound as a white solid (2.43 g, 22%).

Workup

temperaturecooled to room temperature
customThe organic layer was separated
extractionthe aqueous layer was extracted with two further portions of ethyl acetate (25 mL)
washThe combined organic extracts were washed with brine (50 mL)
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe residue was purified
washeluting with 10 to 30% ethyl acetate in heptanes

Sources & evidence

ORD record: ord-e2caf7767c75420d8b991bb22d20dbad
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067922B2

Reaction notes

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