2-Chloro-5-hydroxypyridine → HCID 86642879, compound

HRID 1848921Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].F[C:16]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:17]=1[C:18]([O:20][CH3:21])=[O:19]>CC1CCCO1.CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:16]2[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:17]=2[C:18]([O:20][CH3:21])=[O:19])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-chloropyridin-3-ol (2.41 g) in 2-methyltetrahydrofuran (20 mL) and N,N-dimethylformamide (4 mL) was added potassium tert-butoxide (1.0M in tetrahydrofuran) (18.60 mL). The reaction was stirred for 15 minutes, then methyl 2,4-difluorobenzoate (3.52 g) was added as a solution in 2-methyltetrahydrofuran (2 mL). The reaction was then heated to 80° C. and stirred under a nitrogen atmosphere for 3 days. The reaction was cooled, diluted with ethyl acetate (100 mL), washed with water (50 mL), 1N aqueous HCl (50 mL), and brine (50 mL), dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (Reveleris 80 g), eluting with 10% ethyl acetate/hexanes provided the title compound.

Workup

stirringstirred under a nitrogen atmosphere for 3 days
temperatureThe reaction was cooled
washwashed with water (50 mL), 1N aqueous HCl (50 mL), and brine (50 mL)
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
washSilica gel chromatography (Reveleris 80 g), eluting with 10% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-9573d2db73264f129f1391b6fd40c1d0
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952157B2

Reaction notes

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