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【结 构 式】

【分子编号】53987

【品名】(2S)-3-(4-hydroxyphenyl)-4-methyl-2-{4-[2-(1-piperidinyl)ethoxy]phenyl}-2H-chromene-5,7-diol

【CA登记号】n/a

【 分 子 式 】C29H31NO5

【 分 子 量 】473.56888

【元素组成】C 73.55% H 6.6% N 2.96% O 16.89%

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:(X)

The reaction of 1-(2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)-ethanone (I) with DHP and Ts-OH in ethyl acetate gives the bis-tetrahydropyranyl ether (II), which is condensed with the benzaldehyde (III) by means of piperidine in 2-butanol to yield a mixture of the propenone (IV) and the benzopyranone (V). This mixture, without isolation, is treated with DBU to convert (IV) into (V). The methylation of (V) with MeLi in tert-butyl methyl ether affords the benzopyran-4-ol (VI), which is treated with (S)-(+)-camphorsulfonic acid (VII) to provide the dehydrated benzopyran camphorsulfonate (VIII) as a diastereomeric mixture that is separated by crystallization. The desired isomer (IX) is treated with TEA to give the title compound (X) as free base that is finally treated with HCl in EtOH/water to yield the desired hydrochloride.

1 Gauthier, S.; et al.; Synthesis and structure-activity relationships of analogs of EM-652, a pure selective estrogen receptor modulator. Part 1: Study of nitrogen substitution. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 224.
2 Lu, Y.; Draper, R.W.; Iyer, R.V.; Vater, E.J. (Schering Corp.); Enantioselective synthesis. US 6262270 .
3 Lu, Y.; Draper, R.W.; Iyer, R.V.; Vater, E.J. (Schering Corp.); Enantioselective synthesis. WO 0009493 .
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) 51229 1-(2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)-1-ethanone C14H12O4 详情 详情
(II) 51230 1-[2-hydroxy-4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-2-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-1-ethanone C24H28O6 详情 详情
(III) 35795 4-[2-(1-piperidinyl)ethoxy]benzaldehyde 26815-04-3 C14H19NO2 详情 详情
(IV) 53981 (E)-1-[2-hydroxy-4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-3-{4-[2-(1-piperidinyl)ethoxy]phenyl}-2-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-2-propen-1-one n/a C38H45NO7 详情 详情
(V) 53982 (2R,3S)-5-hydroxy-2-{4-[2-(1-piperidinyl)ethoxy]phenyl}-7-(tetrahydro-2H-pyran-2-yloxy)-3-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-2,3-dihydro-4H-chromen-4-one n/a C38H45NO8 详情 详情
(VI) 53983 (2R,3S)-4-methyl-2-{4-[2-(1-piperidinyl)ethoxy]phenyl}-7-(tetrahydro-2H-pyran-2-yloxy)-3-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-3,4-dihydro-2H-chromene-4,5-diol n/a C39H49NO8 详情 详情
(VII) 53984 (+/-)-Camphor-10-sulphonic acid; (?-10-Camphorsulfonic acid; DL-Camphor-10-sulfonic acid; DL-10-Camphorsulfonic acid; DL-Camphor-10-sulfonic acid; DL-Oxo-10-Bornanesulfonic acid 5872-08-2 C10H16O4S 详情 详情
(VIII) 53985 1-(2-{4-[5,7-dihydroxy-3-(4-hydroxyphenyl)-4-methyl-2H-chromen-2-yl]phenoxy}ethyl)piperidinium (7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonate n/a C39H47NO9S 详情 详情
(IX) 53986 1-(2-{4-[(2S)-5,7-dihydroxy-3-(4-hydroxyphenyl)-4-methyl-2H-chromen-2-yl]phenoxy}ethyl)piperidinium (7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonate n/a C39H47NO9S 详情 详情
(X) 53987 (2S)-3-(4-hydroxyphenyl)-4-methyl-2-{4-[2-(1-piperidinyl)ethoxy]phenyl}-2H-chromene-5,7-diol n/a C29H31NO5 详情 详情
Extended Information