1-Chloro-3,5-dimethoxybenzene → 1-(2-Chloro-4,6-dimethoxyphenyl)-2-(4-methoxyphenyl)ethanone

HRID 1765401Notes

Reaction equation

[Cl-].[Al+3].[Cl-].[Cl-].[CH3:5][O:6][C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[C:9]([O:14][CH3:15])[CH:8]=1.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25](Cl)=[O:26])=[CH:20][CH:19]=1>ClCCCl.[Cl-].[Zn+2].[Cl-]>[Cl:13][C:11]1[CH:12]=[C:7]([O:6][CH3:5])[CH:8]=[C:9]([O:14][CH3:15])[C:10]=1[C:25](=[O:26])[CH2:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=1

Participants

Conditions

Temperature: -25 °C

Procedure

To 1,2-dichloroethane (500 mL) were added anhydrous aluminum chloride (50.5 g) and zinc chloride (5.72 g), followed by stirring for 15 min. Under ice-cooling, a solution of 1,3-dimethoxy-5-chlorobenzene (55 g) in 1,2-dichloroethane (140 mL) was added. The mixture was cooled to −25° C. and 4-methoxyphenylacetyl chloride (53.9 mL) in 1,2-dichloroethane (250 mL) was added drop-wise. The mixture was allowed to warm to room temperature and stirred for 12 h. The mixture was cooled to 0° C., quenched with 1.0 N HCl (300 mL), and the resulting suspension was filtered through Celite and silica gel using ethyl acetate. Chromatography on silica gel (eluant: 10–40% ethyl acetate/hexane) provided the title compound (39 g). 1H NMR (DMSO-d6): 7.07 (d, 2H, J=8.77 Hz), 6.85 (d, 2H, J=8.77 Hz), 6.62 (m, 2H), 3.94 (s, 2H), 3.80 (s, 6H), 3.72 (s, 3H); MS: 321 (MH+).

Workup

temperatureUnder ice-cooling
temperatureto warm to room temperature
stirringstirred for 12 h
temperatureThe mixture was cooled to 0° C.
customquenched with 1.0 N HCl (300 mL)
filtrationthe resulting suspension was filtered through Celite and silica gel

Sources & evidence

ORD record: ord-e4273e2b6962454d8de544093a05ca41
Source dataset: uspto-grants-2007_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07226945B2

Reaction notes

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