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

Temperature

0 °C

To a stirred suspension of 4.7 g (0.019 mol) anhydrous CeCl3 in 30 mL anhydrous THF at 0° C. was added 6 mL of 3.0M CH3MgCl dropwise. Stirred at 0° C. for 45 minutes. Next a solution of 2.5 g (0.015 mol) 4-Acetyl-2-fluoro-benzonitrile in 200 mL anhydrous THF was added dropwise at 0° C. Stirred at 0° C. for 1 hour, then quenched with 2N acetic acid added dropwise. The mixture was poured into 200 mL water and acidified to pH 2 with 2N acetic acid. The aqueous layer was extracted with ethyl acetate (2×200 mL). The ethyl acetate extracts were combined, washed with water (2×40 mL), brine (1×40 mL), dried over MgSO4 and concentrated to give an oil, which was then chromatographed on silica gel eluted with 50% ethyl acetate/50% hexanes to give 1.95 g of an amber oil.

1. stirringStirred at 0° C. for 1 hour
2. customquenched with 2N acetic acid
3. additionadded dropwise
4. additionThe mixture was poured into 200 mL water
5. extractionThe aqueous layer was extracted with ethyl acetate (2×200 mL)
6. washwashed with water (2×40 mL), brine (1×40 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated
9. customto give an oil, which
10. customwas then chromatographed on silica gel
11. washeluted with 50% ethyl acetate/50% hexanes

ORD record

ord-7408e970f93d4611ac1cb16dfa359160

Source dataset

uspto-grants-2005_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06869945B2