Methanol → Methyl 2-(4-fluorophenyl)oxazole-4-carboxylate

HRID 1519223Notes

Reaction equation

FC(F)(F)S(O[C:7]1[N:8]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[O:10][CH:11]=1)(=O)=O.[CH3:21][OH:22].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(N(CC)CC)C.CN([CH:62]=[O:63])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C:9]2[O:10][CH:11]=[C:7]([C:21]([O:63][CH3:62])=[O:22])[N:8]=2)=[CH:13][CH:14]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 2-(4-fluorophenyl)-1,3-oxazol-4-yl trifluoromethanesulfonate (30 g, 96 mmol, WO2010/017079A1) in DMF (200 ml) was added methanol (78 ml, 1928 mmol) followed by palladium (II) acetate (2.164 g, 9.64 mmol) and dppp (3.98 g, 9.64 mmol). Triethylamine (26.9 ml, 193 mmol) was added and the reaction mixture was purged with CO for 3 minutes, placed under balloon pressure of CO, stirred at 65° C. for 2 h, allowed to cool to room temperature and poured onto ice water. The reaction mixture was extracted with DCM, dried over Na2SO4, filtered, concentrated and purified by flash chromatography (silica, 10-50% EtOAc/heptanes) to provide methyl 2-(4-fluorophenyl)-1,3-oxazole-4-carboxylate (7.4 g).

Workup

customthe reaction mixture was purged with CO for 3 minutes
temperatureto cool to room temperature
additionpoured onto ice water
extractionThe reaction mixture was extracted with DCM
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
custompurified by flash chromatography (silica, 10-50% EtOAc/heptanes)

Sources & evidence

ORD record: ord-bb8c32f60186402bb8c89cba2b7b9ed5
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073879B2

Reaction notes

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