Diisopropylethylamine → N-(3-acetyl-4-chlorophenyl)-3,5-dimethoxybenzamide

To a magnetically stirred solution of 2′-chloro-5′-amino-acetophenone (0.72 g, 4.2 mmol) in 20 ml of dichloromethane was added diisopropylethylamine (2.2 ml, 12.6 mmol). 3,5-dimethoxybenzoyl chloride (1.39 g, 6.9 mmol) in a single portion. The reaction was stirred for 2 h at room temperature, and a second portion of 3,5-dimethoxybenzoyl chloride (1.26 g, 6.3 mmol) was added, followed by diisopropylethylamine (1.0 ml, 5.7 mmol). The resulting solution was stirred an additional 3 h, and then quenched by the addition of 30 ml 1N HCl. The layers were separated and the aqueous layer was extracted with EtOAc (3×30 ml). The combined organics were washed with saturated NaHCO3 (1×20 ml), dried with solid anhydrous MgSO4, then concentrated. The crude product was purified by flash column chromatography on silica gel eluting with EtOAc:hexanes (0:1 to 2:5) to afford the desired N-(3-acetyl-4-chlorophenyl)-3,5-dimethoxybenzamide.

1. stirringThe resulting solution was stirred an additional 3 h
2. customquenched by the addition of 30 ml 1N HCl
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with EtOAc (3×30 ml)
5. washThe combined organics were washed with saturated NaHCO3 (1×20 ml)
6. dry with materialdried with solid anhydrous MgSO4
7. concentrationconcentrated
8. customThe crude product was purified by flash column chromatography on silica gel eluting with EtOAc:hexanes (0:1 to 2:5)

ORD record

ord-3a235add62c24d23834f7a1ed0c62c6f

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08273743B2