反应详情

温度

100 °C

A mixture of 4.05 g (18.0 mmol) of 6-(3-chloro-4-hydroxyphenyl)-4,5-dihydro-3(2H)-pyridazinone (prepared as described in Eur. Pat. application EP0 178,189), 4.52 g (21.6 mmol) of methyl 4-bromo-2,2-dimethylbutyrate (prepared by treatment of 2,2-dimethylbutyrolactone with gaseous HBr, conversion to the acid chloride with oxalyl chloride, and treatment with methanol and triethylamine), and 2.99 g (21.6 mmol) of anhydrous K2CO3 in 40 ml of DMF is heated at 100° C. for 4 hrs under N2. The DMF is removed under vacuum, the residue taken up in 300 ml of 50:50 water EtOAc, the organic phase washed with cold 5% NaOH (50 ml), then water (50 ml), and dried (MgSO4) The solvent is removed under vacuum to give an oily residue. The oil is crystallized by the addition of 50 ml of ethyl ether to give 4.75 g of 6-[4 -(3-carbomethoxy-3,3-dimethylpropyloxy)-3-chlorophenyl]-4,5-dihydro-3(2H)-pyridazinone as a white crystalline solid, m.p. 109°-110° C. Yield, 75%.

1. customThe DMF is removed under vacuum
2. washthe organic phase washed with cold 5% NaOH (50 ml)
3. dry with materialwater (50 ml), and dried (MgSO4) The solvent
4. customis removed under vacuum
5. customto give an oily residue
6. customThe oil is crystallized by the addition of 50 ml of ethyl ether