Sodium Carbonate → 5-(4-Cyano-2-fluoro-phenyl)-isoxazole-3-carboxylic acid ethyl ester

HRID 1409712Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9](Cl)[O:8][N:7]=1)=[O:5])[CH3:2].[C:12]([C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[C:16]([F:23])[CH:15]=1)#[N:13].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:17]2[CH:18]=[CH:19][C:14]([C:12]#[N:13])=[CH:15][C:16]=2[F:23])[O:8][N:7]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of 5-chloro-isoxazole-3-carboxylic acid ethyl ester (600 mg), 4-cyano-2-fluorophenylboronic acid (665 mg), and aqueous Na2CO3 solution (2 M; 4.41 mL) in 1,4-dioxane (15 mL) is purged with argon for 15 min prior to the addition of Pd(PPh3)4 (276 mg). The reaction mixture is heated under an argon atmosphere to 140° C. for 20 min in a microwave oven. The solvent is evaporated in vacuo and the residue is mixed with water and ethyl acetate. The aqueous phase is extracted with ethyl acetate and the combined extracts are washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product is purified by silica gel chromatography (cyclohexane/ethyl acetate 80:20→50:50). LC (method 19): tR=1.50 min; Mass spectrum (ESI+): m/z=261 [M+H]+.

Workup

customis purged with argon for 15 min
additionto the addition of Pd(PPh3)4 (276 mg)
customThe solvent is evaporated in vacuo
additionthe residue is mixed with water and ethyl acetate
extractionThe aqueous phase is extracted with ethyl acetate
washthe combined extracts are washed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe crude product is purified by silica gel chromatography (cyclohexane/ethyl acetate 80:20→50:50)

Sources & evidence

ORD record: ord-0b75a2be09cd4024bcffe958208d21c4
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921398B2

Reaction notes

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