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【结 构 式】

【分子编号】19982

【品名】methyl 2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-4,5-dihydro-1,3-oxazole-4-carboxylate

【CA登记号】

【 分 子 式 】C19H27NO4

【 分 子 量 】333.42772

【元素组成】C 68.44% H 8.16% N 4.2% O 19.19%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IV)

1) The N-acylation of DL-serine (I) with 3,5-di-tert-butyl-4-hydroxybenzoic acid by means of carbonyldiimidazole (CDI) in THF gives the acylated serine (III), which is cyclized by means of CBr4/triphenylphosphine/imidazole in acetonitrile to yields the oxazoline (IV). The dehydrogenation of (IV) with activated MnO2 in acetone affords 2-(3,5-di-tert-butyl-4-hydroxyphenyl)oxazole-4-carboxylic acid methyl ester (V), which is reduced with LiBH4 in THF/methanol giving the oxazolylmethnaol (VI). The reaction of (VI) with Br2/triphenylphosphine in acetonitrile yields the bromomethyl derivtive (VII), which is condensed with N-ethyl-N-[2-(4-hydroxyphenyl)ethyl]formamide (VIII) by means of NaH in THF to afford the formylated precursor (IX). Finally, this compound is converted into LY-382924 by reduction of the formyl group with AlH3 (LiAlH4/H2SO4) in THF and treatmnt with HCl gas in CHCl3. 2) The intermediate N-ethyl-N-[2-(4-hydroxyphenyl)ethyl]formamide (VIII) has been obtained as follows: The acylation of 2-(4-hydroxyphenyl)ethylamine (X) with acetic anhydride gives the acetamide (XI), which is reduced with LiAlH4 to the secondary amine (XII). Finally, this amine is formylated with formic acid and carbonyldiimidazole (CDI) in THF.

1 Heinz, L.J.; et al.; Synthesis and biological evaluation of a novel series of antioxidants for the treatment of global cerebral ischemia. 217th ACS Natl Meet (March 21 1999, Anaheim) 1998, Abst MEDI 130.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 14224 Serine, methyl ester; methyl 2-amino-3-hydroxypropanoate 2104-89-4 C4H9NO3 详情 详情
(II) 19980 3,5-di(tert-butyl)-4-hydroxybenzoic acid 1421-49-4 C15H22O3 详情 详情
(III) 19981 methyl 2-[[3,5-di(tert-butyl)-4-hydroxybenzoyl]amino]-3-hydroxypropanoate C19H29NO5 详情 详情
(IV) 19982 methyl 2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-4,5-dihydro-1,3-oxazole-4-carboxylate C19H27NO4 详情 详情
(V) 19983 methyl 2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazole-4-carboxylate C19H25NO4 详情 详情
(VI) 19984 2,6-di(tert-butyl)-4-[4-(hydroxymethyl)-1,3-oxazol-2-yl]phenol C18H25NO3 详情 详情
(VII) 19985 4-[4-(bromomethyl)-1,3-oxazol-2-yl]-2,6-di(tert-butyl)phenol C18H24BrNO2 详情 详情
(VIII) 19986 ethyl(4-hydroxyphenethyl)formamide C11H15NO2 详情 详情
(IX) 19987 4-([2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]methoxy)phenethyl(ethyl)formamide C29H38N2O4 详情 详情
(X) 19988 4-(2-Aminoethyl)phenol; Tyramine 51-67-2 C8H11NO 详情 详情
(XI) 19989 N-(4-hydroxyphenethyl)acetamide C10H13NO2 详情 详情
(XII) 19990 4-[2-(ethylamino)ethyl]phenol C10H15NO 详情 详情
Extended Information