Potassium Phosphate, Tribasic → 6-Cyclopropylpyridine-3-carbonitrile

HRID 1919799Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][N:3]=1.[CH:10]1(B(O)O)[CH2:12][CH2:11]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:10]1([C:2]2[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][N:3]=2)[CH2:12][CH2:11]1

Participants

Conditions

Temperature: 100 °C

Procedure

Deoxygenate a mixture of 2-bromo-5-cyanopyridine (1.83 g, 10.0 mmol), cyclopropylboronic acid (1.1 g, 13 mmol), palladium(II) acetate (0.11 g, 0.49 mmol), and potassium phosphate (7.4 g, 35 mmol) in toluene (40.00 mL) and water (2 mL) by bubbling nitrogen through the mixture. Add tricyclohexylphosphine (1.0 mL, 1.0 mmol, 1 M in toluene). Heat the reaction mixture at 100° C. for 14 hours and allow the reaction mixture to cool. Decant the supernatant and wash the leftover sludge with dichloromethane. Concentrate the combined organics in vacuo. Purify by silica gel chromatography (0-5% ethyl acetate/hexane) to afford the titled compound as a white crystalline solid (774 mg, 47%). 1H NMR (400 MHz, CDCl3) δ 1.08 (m, 4H), 2.05 (m, 1H), 7.23 (dd, J=8.2, 1.0 Hz, 1H), 7.73 (dd, J=8.0, 2.4 Hz, 1H), 8.66 (d, J=1.2 Hz, 1H).

Workup

customDeoxygenate
customby bubbling nitrogen through the mixture
temperatureto cool
customDecant the supernatant
washwash the leftover sludge with dichloromethane
concentrationConcentrate the combined organics in vacuo
customPurify by silica gel chromatography (0-5% ethyl acetate/hexane)

Sources & evidence

ORD record: ord-c5996eb5f07645519fc0dda666324d2e
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08168659B2

Reaction notes

Loading…