Potassium Carbonate → 2-Chloro-3-fluoro-5-vinylpyridine

HRID 920136Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([F:9])[C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:10][C:11]1(C)C(C)(C)OB(C=C)O1.C([O-])([O-])=O.[K+].[K+]>CCO.C1COCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:8][C:5]1[C:4]([F:9])=[CH:3][C:2]([CH:10]=[CH2:11])=[CH:7][N:6]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 101 (5.00 g, 23.8 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (119, 21.39 mmol, Sigma-Aldrich) in a mixture of EtOH (30.0 mL) and THF (64.0 mL) under an argon atmosphere was added Pd(PPh3)2Cl2 (1.33 g, 1.90 mmol) and K2CO3 (8.20 g, 59.4 mmol). The resulting reaction mixture was heated to 60° C. and held for 16 hrs in a sealed bottle. The mixture was cooled to a temperature of about 25° C., diluted with water, and extracted with EtOAc. The organic layer was separated, washed with brine, and concentrated. The residue was chromatographed on a silica gel column eluted with EtOAc:hexanes to provide 112 as a colorless oil (85% yield). 1H NMR (CDCl3) δ: 5.48 (1H, d, J=10.97 Hz), 5.83 (1H, d, J=17.62 Hz), 6.68 (1H, dd, J=10.97, 17.62 Hz), 7.52 (1H, d, J=1.60 Hz), 8.20 (1H, d, J=1.60 Hz). LC/MS (M+1): m/z=158.

Workup

customThe resulting reaction mixture
temperatureThe mixture was cooled to a temperature of about 25° C.
extractionextracted with EtOAc
customThe organic layer was separated
washwashed with brine
concentrationconcentrated
customThe residue was chromatographed on a silica gel column
washeluted with EtOAc

Sources & evidence

ORD record: ord-6b3a143d913644f48537097df814dd51
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273043B2

Reaction notes

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