2',4'-Dichlorovalerophenone synthesis

Yield:-

Reaction Conditions:

Stage #1: N-methoxy-N-methyl-2,4-dichlorobenzamide;n-butyllithium in tetrahydrofuran at 20; for 4 h;
Stage #2: with hydrogenchloride in tetrahydrofuran;water;ethyl acetate;

Steps:

Intermediate GA1-(2,4-Dichloro-phenyl)-pentan-1-one To a stirring hazy solution of 2,4-dichloro-N-methoxy-N-methylbenzenecarboxamide (1 g, 4.27 mmol), in THF (20 ml) is added BuLi (2.051 ml, 5.13 mmol) in portions. The reaction is stirred for 4 hours at RT and the partitioned between 1M HCl (100 ml) and EtOAc (140 ml). The organic portion is washed with brine, dried over Na₂SO₄, and concentrated in vacuo. The crude product is purified by ISCO combiflash chromatography eluting with 0 to 100% EtOAc/iso-hexane on a 40 g silica-column to yield 1-(2,4-dichloro-phenyl)-pentan-1-one as a brown oil; ¹H NMR (400 MHz, CDCl₃) δ 7.45 (1H, d, J 2.0), 7.43 (1H, d, J 7.3), 7.32 (1H, dd, J 7.3, 2.0), 2.94 (2H, t, J 7.4), 1.70 (2H, m), 1.40 (2H, m), 0.95 (3H, t, J 7.3).

References:

US2010/35874,2010,A1 Location in patent:Page/Page column 63; 64