4-{4-[2-(2-Hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-but-2-enoic acid ethyl ester → 4-Hydroxy-1-{4-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-methyl-pent-2-en-1-one

HRID 2062188Notes

Reaction equation

C(OC(=O)[CH:5]=[CH:6][C:7]([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[C:24]3[C:19](=[CH:20][C:21]([CH3:25])=[CH:22][CH:23]=3)[N:18]=[C:17]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[OH:32])[N:16]=2)[CH2:11][CH2:10]1)=[O:8])C.C[Mg]Br>C(OCC)C.O.C(Cl)Cl>[OH:32][C:27]([CH3:28])([CH3:26])[CH:5]=[CH:6][C:7]([N:9]1[CH2:10][CH2:11][N:12]([C:15]2[C:24]3[C:19](=[CH:20][C:21]([CH3:25])=[CH:22][CH:23]=3)[N:18]=[C:17]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[OH:32])[N:16]=2)[CH2:13][CH2:14]1)=[O:8]

Participants

Conditions

Temperature: 0 °C

Procedure

To 4-{4-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-but-2-enoic acid ethyl ester (655 mg, 1.47 mmol) in 2 mL of diethyl ether at −20° C. was added methyl magnesium bromide (8.4 mL, 11.7 mmol, 1.4 M THF/Toluene), and the reaction mixture was allowed to warm to 0° C. over 15 minutes The mixture was diluted with 10 mL of water and 15 mL of CH2Cl2. The resulting emulsion was filtered, and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure to give the alcohol. LC/MS: m/z 433.5 (M+H)+ at 2.56 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

filtrationThe resulting emulsion was filtered
customthe organic layer was separated
dry with materialdried over Na2SO4
customThe solvent was removed under reduced pressure

Sources & evidence

ORD record: ord-c651314df6bd4f008bc12e6010d1ec56
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08283354B2

Reaction notes

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