Hydrochloric Acid → 2-Fluoro-4-formylbenzonitrile

A solution of 4-bromo-2-fluorobenzonitrile (5.00 g, 25 mmol) in dry THF (50 mL) at −10° C. under argon was treated with a solution of isopropylmagnesium chloride (2M in THF, 15.0 mL, 30.0 mmol) dropwise before stirring at this temperature for 3 h. A solution of N-formylpiperidine (3.89 g, 35.0 mmol) in dry THF (15 mL) was added dropwise and the mixture allowed to warm to room temperature before stirring for 1.5 h. The resultant solution was treated with 4M aq HCl (250 mL each) and the organics extracted with EtOAc. The combined organics were dried (MgSO4), filtered and evaporated before purification of the residue by column chromatography (SiO2; eluting with 30% to 50% EtOAc in cyclohexane) to afford 2-fluoro-4-formyl-benzonitrile VII-a as a pale yellow solid (2.73 g, 73%). 1H NMR (300 MHz, CDCl3) δ 10.07 (d, J=1.7 Hz, 1H), 7.90-7.79 (m, 2H), 7.74 (dd, J=8.5, 0.8 Hz, 1H).

1. stirringbefore stirring for 1.5 h
2. extractionthe organics extracted with EtOAc
3. dry with materialThe combined organics were dried (MgSO4)
4. filtrationfiltered
5. customevaporated before purification of the residue by column chromatography (SiO2; eluting with 30% to 50% EtOAc in cyclohexane)

ORD record

ord-4bab359f1c7b4f6795aea578e88d75a0

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09168245B2