【结 构 式】 |
【分子编号】26082 【品名】(E)-2-methyl-7-phenyl-2-heptenoic acid 【CA登记号】 |
【 分 子 式 】C14H18O2 【 分 子 量 】218.29572 【元素组成】C 77.03% H 8.31% O 14.66% |
合成路线1
该中间体在本合成路线中的序号:(IV)The reaction of 5-phenylpentanal (I) with triethyl 2-phosphonopropionate (II) by means of NaOEt in THF gives ethyl 2-methyl-7-phenyl-2(E)-heptenoate (III), which is hydrolyzed with NaOH in methanol/water to the corresponding free acid (IV). The reaction of (IV) with 4-methoxythiophenol (V) in hot piperidine affords 3-(4-methoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid (VI), which by reaction first with oxalyl chloride, then with O-trimethylsilylhydroxylamine (VII) in dichloromethane, and finally with HCl is converted into the hydroxamic acid (VIII). Finally, this compound is oxidized with oxone in methanol/water to provide the target compound as mixture of diastereomeric racemates that is separated by reversed phase HPLC.
【1】 Groneberg, R.D.; Neuenschwander, K.W.; Djuric, S.W.; McGeehan, G.M.; Burns, C.J.; Condon, S.M.; Morrissette, M.M.; Salvino, J.M.; Scotese, A.C.; Ullrich, J.W. (Aventis Pharma SA); Substd. (aryl, heteroaryl, arylmethyl or heteroarylmethyl) hydroxamic acid cpds.. EP 0871439; JP 2000503012; WO 9724117 . |
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) | 25636 | 5-phenylpentanal | C11H14O | 详情 | 详情 | |
(II) | 18816 | ethyl 2-(diethoxyphosphoryl)propanoate | 3699-66-9 | C9H19O5P | 详情 | 详情 |
(III) | 26081 | ethyl (E)-2-methyl-7-phenyl-2-heptenoate | C16H22O2 | 详情 | 详情 | |
(IV) | 26082 | (E)-2-methyl-7-phenyl-2-heptenoic acid | C14H18O2 | 详情 | 详情 | |
(V) | 25639 | 4-methoxyphenylhydrosulfide; 4-methoxybenzenethiol | 34320-82-6 | C7H8OS | 详情 | 详情 |
(VI) | 26083 | 3-[(4-methoxyphenyl)sulfanyl]-2-methyl-7-phenylheptanoic acid | C21H26O3S | 详情 | 详情 | |
(VII) | 26091 | O-(trimethylsilyl)hydroxylamine; (aminooxy)(trimethyl)silane | 22737-36-6 | C3H11NOSi | 详情 | 详情 |
(VIII) | 26084 | N-hydroxy-3-[(4-methoxyphenyl)sulfanyl]-2-methyl-7-phenylheptanamide | C21H27NO3S | 详情 | 详情 |