4-Acetyl-2-fluorobenzonitrile → 2-Fluoro-4-(2-hydroxypropan-2-yl)benzonitrile

HRID 844018

Reaction equation

[CH3:1][Mg]Cl.[C:4]([C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[C:9]([F:15])[CH:8]=1)(=[O:6])[CH3:5]>O1CCCC1>[F:15][C:9]1[CH:8]=[C:7]([C:4]([OH:6])([CH3:1])[CH3:5])[CH:14]=[CH:13][C:10]=1[C:11]#[N:12]

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred suspension of CeCl3 (4.7 grams, 19.0 mmole) in tetrahydrofuran (30 ml) at 0° C. was added dropwise 3.0 M methyl magnesium chloride (6.0 ml, 19.0 mmole). The mixture was stirred at 0° C. for 45 minutes and 4-Acetyl-2-fluoro-benzonitrile (2.5 grams, 15.0 mmole) in tetrahydrofuran (20 ml) was added dropwise. The mixture was stirred at 0° C. for 1 hour and quenched with 5 ml 2 N acetic acid added dropwise. The mixture was poured into 200 ml water, acidified to pH 2 with 2 N acetic acid and extracted with ethyl acetate. The combined extracts were washed with water and brine, dried over magnesium sulfate and concentrated to give an oil which was purified via flash chromatography on silica using 50% ethyl acetate/hexane as eluent to give an oil (1.95 g). MW 179.21; MS (m/e) 179 (M+).

Workup

stirringThe mixture was stirred at 0° C. for 1 hour
customquenched with 5 ml 2 N acetic acid
additionadded dropwise
additionThe mixture was poured into 200 ml water
extractionextracted with ethyl acetate
washThe combined extracts were washed with water and brine
dry with materialdried over magnesium sulfate
concentrationconcentrated
customto give an oil which
customwas purified via flash chromatography on silica using 50% ethyl acetate/hexane as eluent

Sources & evidence

ORD record: ord-2554200d4c05417e9dd78dcec289badc
Source dataset: uspto-grants-2002_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06380218B1

Linked notes

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