(+-)-2-Butanol → Tert-butyl 2-(2',3-difluoro-2,4'-bipyridin-5-yl)acetate

HRID 592232Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:4][C:3]=1[F:16].[F:17][C:18]1[CH:23]=[C:22](B(O)O)[CH:21]=[CH:20][N:19]=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:17][C:18]1[CH:23]=[C:22]([C:2]2[C:3]([F:16])=[CH:4][C:5]([CH2:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:6][N:7]=2)[CH:21]=[CH:20][N:19]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a flask containing tert-butyl 2-(6-chloro-5-fluoropyridin-3-yl)acetate 205-3 (370 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 20% ethyl acetate in dichloromethane to give tert-butyl 2-(2′,3-difluoro-2,4′-bipyridin-5-yl)acetate 205-5 as a yellow oil. MS m/z 307.1 (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 20% ethyl acetate in dichloromethane

Sources & evidence

ORD record: ord-ee07272eab064ac0b4966be651c71226
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238646B2

Reaction notes

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