Benzyl Alcohol → Benzyl 4-fluorobenzoate

A mixture of 4-fluorobenzoic acid (5.0 g, 36 mmol) in CH2Cl2 was treated with oxallyl chloride (6.2 mL, 72 mmol) and a catalytic amount of DMF. The mixture was stirred until the evolution of gas stopped and then concentrated under reduced pressure. The residue was re-dissolved in CH2Cl2 and the solution was added in a drop wise manner to a mixture of benzyl alcohol (3.9 g, 36 mmol), diisopropyl ethyl amine (12.6 mL, 72 mmol) and a catalytic amount of DMAP in CH2Cl2. After stirring overnight the reaction mixture was concentrated and the residue was passed through a silica gel plug with 10% Et2O in hexanes. The intermediate 4-fluoro benzoic acid benzyl ester obtained from the above procedure was dissolved in DMSO (25 mL). Followed addition of piperazine (14 g, and the mixture was heated in a sealed tube at 120° C. overnight. Next morning the reaction mixture was partitioned between EtOAc and water. The water layer was basified to pH 12 with solid NaOH, extracted once again with EtOAc and the combined EtOAc layer was dried over Na2SO4, filtered and concentrated to afford the product (8.5 g, Yield: 80%). HRMS m/z calcd for C18H20N2O2 [M+H]: 297.1598. Found: 297.1597.

1. concentrationconcentrated under reduced pressure
2. dissolutionThe residue was re-dissolved in CH2Cl2
3. stirringAfter stirring overnight the reaction mixture
4. concentrationwas concentrated

ORD record

ord-8da57f37b3d84ac4b9cb064839318378

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324385B2