Preparation method of olaparib key intermediate

The invention provides a preparation method of an olaparib key intermediates 4-(3-bromo-4-fluorobenzyl)phthalazin-1(2H)-one (a compound shown as a formula IV) and 2-fluoro-5-[(4-oxo-3,4-dihydro-1-phthalazinyl)methyl]benzoic acid (a compound shown as a formula V). Specifically, (3-oxo-1,3-dihydroisobenzofuran-1-yl)phosphonic acid dimethyl ester is used as a raw material to be subjected to a Wittig-Horner reaction with 3-bromo-4-fluorobenzaldehyde to obtain a formula III, the formula III and hydrazine hydrate are subjected to cyclization to obtain a formula IV, and the formula IV is subjected toa reaction with n-butyllithium and carbon dioxide to obtain an olaparib intermediate V. The method is economical and environment-friendly, and the yield is greatly improved. 本发明提供了一种奥拉帕尼关键中间体式(4-(3-溴-4-氟苄基)-二氮杂萘-1(2H)-酮(式Ⅳ化合物)和5-[(3,4-二氢-4-氧代-1-酞嗪基)甲基]-2-氟苯甲酸(式Ⅴ化合物)的制备方法。具体地，以(3-氧代-1,3-二氢异苯并呋喃-1-基)膦酸二甲酯为原料与3-溴-4-氟苯甲醛发生Wittig-Horner反应，得到式Ⅲ，式Ⅲ与水合肼环合得到式Ⅳ，式Ⅳ与正丁基锂、二氧化碳反应得到奥拉帕尼中间体Ⅴ。本发明经济环保，且收率大大提高。