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【结 构 式】 
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【分子编号】35213 【品名】4-(7-methoxy-3-phenyl-2H-chromen-4-yl)phenol 【CA登记号】 |
【 分 子 式 】C22H18O3 【 分 子 量 】330.38312 【元素组成】C 79.98% H 5.49% O 14.53% |
合成路线1
该中间体在本合成路线中的序号：(IV)Coumarin (III) was prepared by condensation of benzophenone (I) with phenylacetic acid (II) in the presence of Ac2O and Et3N. Reduction of the lactone function of (III) with LiAlH4, followed by acidic treatment furnished diaryl chromene (IV). Subsequent hydrogenation of (IV) over Pd/C gave rise to the racemic cis chromane (V), which was O-alkylated with 1-(2-chloroethyl) pyrrolidine (VI) producing the corresponding (pyrrolidinyl)ethoxy derivative. Resolution by means of active ditoluoyl tartaric acid yielded the desired (-)-enantiomer (VII). Finally, cleavage of the methoxy group using pyridine hydrochloride at 150 C provided the title compound.
| 【1】 Bury, P.S.; et al.; Synthesis and pharmacological evaluation of novel cis-3,4-diaryl-hydroxychromanes as high affinity partial agonists for the estrogen receptor. Bioorg Med Chem 2002, 10, 1, 125. |
| 【2】 Jacobsen, P.; Treppendahl, S.; Stanley Bury, P.; Kanstrup, A.; Brown Christiansen, L. (Novo Nordisk A/S); Novel cis-3,4-chroman derivs. useful in the prevention or treatment of estrogen related diseases or syndromes. EP 0937060; WO 9818776 . |
| 【3】 Jacobsen, P.; Treppendahl, S.; Stanley Bury, P.; Kanstrup, A.; Brown Christiansen, L. (Novo Nordisk A/S); Novel (-)-enantiomers of cis-3,4-chroman derivs. useful in the prevention or treatment of estrogen related diseases or syndromes. EP 0937057; WO 9818771 . |
| 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) | 35211 | (2-hydroxy-4-methoxyphenyl)(4-hydroxyphenyl)methanone | C14H12O4 | 详情 | 详情 | |
| (II) | 16148 | Benzeneacetic acid; 2-Phenylacetic acid; Phenyl Acetic Acid | 103-82-2 | C8H8O2 | 详情 | 详情 |
| (III) | 35212 | 4-(7-methoxy-2-oxo-3-phenyl-2H-chromen-4-yl)phenyl acetate | C24H18O5 | 详情 | 详情 | |
| (IV) | 35213 | 4-(7-methoxy-3-phenyl-2H-chromen-4-yl)phenol | C22H18O3 | 详情 | 详情 | |
| (V) | 35214 | 4-[(3S,4R)-7-methoxy-3-phenyl-3,4-dihydro-2H-chromen-4-yl]phenol | C22H20O3 | 详情 | 详情 | |
| (VI) | 33922 | 1-(2-Chloroethyl)pyrrolidine; N-(2-Chloroethyl)pyrrolidine | C6H12ClN | 详情 | 详情 | |
| (VII) | 35215 | 1-(2-[4-[(3S,4R)-7-methoxy-3-phenyl-3,4-dihydro-2H-chromen-4-yl]phenoxy]ethyl)pyrrolidine; 4-[(3S,4R)-7-methoxy-3-phenyl-3,4-dihydro-2H-chromen-4-yl]phenyl 2-(1-pyrrolidinyl)ethyl ether | C28H31NO3 | 详情 | 详情 |