2-BROMO-1-(5-CHLORO-2-METHOXY-PHENYL)-ETHANONE

Combine 5'-chloro-2'-hydroxyacetophenone (17.0 g, 100 mmol) with potassium carbonate (15.1 g, 109 mmol) and iodomethane (12.5 ML, 200 mmol) in DMF and stir in a sealed vessel overnight at RT. Remove DMF and partition the residue between water and EtOAc. Dry the combined extracts over NA2S04 and concentrate. Chromatograph the resulting residue over silica gel (EtOAc/hexanes) to allow for isolation of 1- (5- Chloro-2-methoxy-phenyl) -ethanone (17.1 g, 93 percent). MS (ES): (M+1) + 185.1, 187.1 M/Z. Dissolve 1- (5-CHLORO-2-METHOXY-PHENYL)-ETHANONE (8. 5 g, 46.2 mmol) in CHC13 (40 mL) and add this mixture to a warmed slurry of CuBr2 (20.6 g, 92.4 mmol) in EtOAc (150 mL). Heat the resulting mixture near reflux for approx. 3 h. Cool and filter the mixture and concentrate the resulting filtrate. Chromatograph the resulting residue over silica gel (CH2CL2) to allow for isolation of 2-bromo-1- (5-chloro-2-methoxy-phenyl)- ethanone (12.0 g, 99 percent). MS (ES): (M+1) + 185. 1, 187. 1 m/z.A solution of 2M borane dimethylsulfide in tetrahydrofuran (65.5ml, 131 mmol) and (3a'S)- 3', 3'-diphenylhexahydrospiro[[1 , 3, 2]dioxaborolane-2, 1 '-pyrrolo[1 , 2-c][1 , 3, 2]oxazaborol]-7'- ium-6-uide (4.29 g, 1 1 .95 mmol) was stirred at room temperature for 30 min under a nitrogen atmosphere. This mixture was then added to a solution of 2-bromo-1 -(5-chloro-2- methoxyphenyl)ethanone (35 g, 120 mmol) in 175ml of tetrhydrofuran over a 5 hour time period. The reaction mixture was then stirred at 25 C for 16h. The reaction mixture was quenched with water, partitioned between ethyl acetate 300 mL . The organic phase was washed with saturated brine 50 mL, water 50 mL , evaporated in vacuo to give the crude products as a yellow oil. The crude residue was purified by flash chromatography on silica gel (petroleum ether/EtOAc = 20/1 ) to give (S)-2-bromo-1 -(5-chloro-2-methoxyphenyl)ethanol (25 g, 85 mmol, 90 % purity, 70.9 % yield) as an orange solid, m/z: [M - OH]+ Calcd for C9Hn BrCI02 247.0; Found 247To a solution of

Molecular Weight:263.51
XLogP3:3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:261.93962
Monoisotopic Mass:261.93962
Topological Polar Surface Area:26.3
Heavy Atom Count:13
Complexity:187
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes