Ethanone, 1-(2-chlorophenyl)- → 2-[4-Chloro-3-(methyloxy)phenyl]-1-(2-chlorophenyl)-ethanone

HRID 1673253

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:10])[CH3:9].Br[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([O:19][CH3:20])[CH:13]=1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2C)CCCCC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:9][C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])=[O:10])=[CH:13][C:14]=1[O:19][CH3:20]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 1-(2-chlorophenyl)ethanone (1.4 mL, 10.8 mmol), 4-bromo-1-chloro-2-(methyloxy)benzene (2.0 g, 9.0 mmol), sodium tert-butoxide (2.2 g, 22.6 mmol), palladium(II) acetate (20.3 mg, 0.1 mmol), and 2-(dicyclohexylphosphino)-2′-methylbiphenyl (65.8 mg, 0.2 mmol) in 30 mL of toluene was degassed and stirred at 80° C. for 16 h. The reaction mixture was cooled and a mixture of Et2O (100 mL) and H2O (100 mL) was added. The aq layer was separated and extracted with Et2O (3×50 mL). Organic layers were combined, dried over MgSO4, and concentrated. Chromatography on a Biotage 40+M cartridge using 1:9 v/v EtOAc/hexanes as the eluant afforded the product: 1H NMR δ 3.87 (s, 3H), 4.22 (s, 2H), 6.75 (dd, J=1.7, 8.2, 1H), 6.81 (d, J=1.6, 1H), 7.26-7.31 (m, 2H), 7.37-7.43 (m, 3H).

Workup

customwas degassed
temperatureThe reaction mixture was cooled
additiona mixture of Et2O (100 mL) and H2O (100 mL)
additionwas added
customThe aq layer was separated
extractionextracted with Et2O (3×50 mL)
dry with materialdried over MgSO4
concentrationconcentrated
customafforded the product

Sources & evidence

ORD record: ord-232b8803963f40f0a7456c432aca91f1
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07999107B2

Linked notes

Loading…