1-(2-Chloro-4-fluorophenyl)ethanone

Methylmagnesium bromide (13.48g, 113.04mmol) was added dropwise to a solution of Example 144A (12.30g, 56.52mmol) in tetrahydrofuran (100.00mL) at - 78°C over 30 minutes, and the mixture was stirred at 0°C for 5 hours.The mixture was added with saturated aqueous ammonium chloride solution (100mL), diluted with water (50mL), extractedwith ethyl acetate (200mL33) and washed with brine (400 mL32). The organic phases were combined, driedover anhydrous sodium sulfate, filtered, the filtrate was concentrated in vacuo and the residue was purified by columnchromatography to give Example 143B as a colorless oil (9.60g, yield 98.42percent).1H NMR (400 MHz, CHLOROFORM-d) 7.64 (dd, J=6.02, 8.53 Hz, 1H), 7.17 (dd, J=2.38, 8.41 Hz, 1H), 7.01-7.07 (m, 1H), 2.61-2.67 (m, 3H).General procedure: Sodium hydride (1.20 g, 30 mmol, c 60% in oil) was added in portions to a stirred mixture of 2?-chloroacetophenone (2.32 g, 15 mmol), N, N-dimethylformamide (15 mL), toluene (10 mL) and carbon disulfide (2.28 g, 30 mmol) keeping the reaction temperature between 15-20 C. After additional 30 min, methanol (0.4 mL) was carefully added and stirring continued for 30 min. After evaporation of toluene under reduced pressure, the residue was heated until the internal temperature reached 125-130 C, maintained at 125-130 C for 30 min, cooled and diluted with water (50 mL). After the addition of acetic acid (1.5 mL) and extraction with ether (2 × 50 mL), the aqueous phase was separated, filtered and acidified with conc. HCl to pH 1. The precipitate was filtrated, washed with water, and dried to give 1.94 g of a yellow solid which was used in the next step without purification. To a magnetically stirred solution of the above obtained solid (1.94 g, 10 mmol) and Et3N (2.00 g, 20 mmol) in CH2Cl2 (50 mL) was added iodoethane (1.55 g, 10 mmol). The reaction mixture was stirred for 1 h at 35 C. After cooling to room temperature, the reaction mixture was poured into 1 N HCl (50 mL). The organic phase was washed with H2O (50 mL), brine (50 mL), and then evaporated under reduced pressure. The residue was purified by column chromatography (EtOAc/PE 1:4) to give the title compound 1a (2.12 g, 64% over two steps). To a magnetically stirred solution of 1a (1.11 g, 5 mmol) in AcOH (5 mL) was added 1 M H2O2/AcOH (6 mL, 1.2 equiv) and the reaction mixture was stirred at 60 C overnight. The reaction solution was poured into water (25 mL) and extracted with dichloromethane (2 ×25 mL). The organic extract was washed with water (50 mL), saturated NaHCO3 (25 mL), brine (25 mL), dried over Na2SO4 and then evaporated. The crude material was purified by recrystallization (hexane/EtOAc 5:2) to give the title compound 2a (1.05 g, 88%). The corresponding compounds 1b-h and 2b-h were prepared according to the general procedure A. The title compound 3a was prepared using 5.0 equiv hydrogen peroxide following general procedure A.

Molecular Weight:172.58
XLogP3:2.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:172.0091207
Monoisotopic Mass:172.0091207
Topological Polar Surface Area:17.1
Heavy Atom Count:11
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes