(+-)-2-Butanol → Ethyl 2-(2'-fluoro-2,4'-bipyridin-5-yl)acetate

HRID 592241Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.[F:14][C:15]1[CH:20]=[C:19](B(O)O)[CH:18]=[CH:17][N:16]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(O)CC>C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:14][C:15]1[CH:20]=[C:19]([C:2]2[CH:3]=[CH:4][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:6][N:7]=2)[CH:18]=[CH:17][N:16]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a flask containing ethyl 2-(6-chloropyridin-3-yl)acetate 208-1 (300 mg, 1.5 mmol), 2-fluoropyridin-4-ylboronic acid 205-4 (318 mg, 2.25 mmol), Pd(OAc)2 (17 mg, 0.075 mmol.), 2-dicyclohexylphosphino-2′,6′-dimethoxyybiphenyl (62 mg, 0.15 mmol), K3PO4 (800 mg, 9 mmol) under argon was added 2-butanol (1.5 mL). The reaction mixture was stirred at 100° C. for 10 hours. After cooled to room temperature, the mixture was diluted with ethyl acetate, washed with water and brine, dried over Na2SO4, and concentrated to dryness by rotary evaporation. The crude was purified by silica gel flash chromatography, eluted with 40% ethyl acetate in dichloromethane to give ethyl 2-(2′-fluoro-2,4′-bipyridin-5-yl)acetate 208-2 as a yellow solid. MS m/z 261.1 (M+1).

Workup

temperatureAfter cooled to room temperature
washwashed with water and brine
dry with materialdried over Na2SO4
concentrationconcentrated to dryness by rotary evaporation
customThe crude was purified by silica gel flash chromatography
washeluted with 40% ethyl acetate in dichloromethane

Sources & evidence

ORD record: ord-7ea0ef85ea28427ab673e6ac3b12cd66
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238646B2

Reaction notes

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