Ethanol → 3-(4-Fluorophenyl)-imidazo[1,5-a]pyridine-8-carboxylic acid ethyl ester

HRID 1423013Notes

Reaction equation

Br[C:2]1[C:3]2[N:4]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=2)[CH:5]=[CH:6][CH:7]=1.CCN([CH2:23][CH3:24])CC.[C]=[O:26].[CH2:27]([OH:29])C>[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[Fe+2]>[CH2:23]([O:26][C:27]([C:2]1[C:3]2[N:4]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=2)[CH:5]=[CH:6][CH:7]=1)=[O:29])[CH3:24]

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of 8-bromo-3-(4-fluorophenyl)-imidazo[1,5-a]pyridine (355 mg, 1.22 mmol), Et3N (330 μL, 2.5 mmol), Pd[PhCN]2Cl2 (11 mg, 0.029 mmol), and 1,1-bis(diphenylphosphino)ferrocene (dppf) (42 mg, 0.076 mmol) in absolute ethanol (15 mL) is placed in a pressure reactor with stirring and placed under 15 bars of carbon monoxide and warmed at 140° C. After 4 hours, the pressure reactor is cooled to room temperature, returned to atmospheric pressure and opened. The reaction mixture is concentrated in vacuo, the resulting residue is dissolved in dichloromethane and passed through a pad of silica gel eluting with ethyl ether to afford 3-(4-fluorophenyl)-imidazo[1,5-a]pyridine-8-carboxylic acid ethyl ester.

Workup

customis placed in a pressure reactor
temperaturethe pressure reactor is cooled to room temperature
concentrationThe reaction mixture is concentrated in vacuo
dissolutionthe resulting residue is dissolved in dichloromethane

Sources & evidence

ORD record: ord-45eef0d15f8d441a87d2bf10e7d2cd84
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927550B2

Reaction notes

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