|
【结 构 式】 
|
【分子编号】25955 【品名】2-(3,5-difluorophenyl)-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one 【CA登记号】 |
【 分 子 式 】C18H14F2OS 【 分 子 量 】316.3713664 【元素组成】C 68.34% H 4.46% F 12.01% O 5.06% S 10.14% |
合成路线1
该中间体在本合成路线中的序号：(VII)The bromination of 2-cyclopentenone (I) gives 2-bromocyclopentenone (II), which is condensed with 3,5-difluorophenylboronic acid (III) by means of a Pd catalyst yielding 2-(3,5-difluorophenyl)-2-cyclopentenone (IV). The reaction of (IV) with the aryl lithium (V) affords the cyclopentenol derivative (VI), which is submitted to an oxidation with PDC with simultaneous allylic transposition to give 2-(3,5-difluorophenyl)-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one (VII). Finally, this compound is oxidized with H 2O2 (Na2WO4) to the target sulfone. The preceding synthetic approach can also be performed with 2-iodo-2-cyclopentenone (obtained by iodination of (I) instead of its bromo analogue (II). The synthetic approaches can also be performed with the arylmagnesium analogue of lithium derivative (V).
| 【1】 Black, C. (Merck Frosst Canada Inc.); 2-(3,5-Difluorophenyl)-3-(4-(methyl-sulfonyl)phenyl)-2-cyclopenten-1-one useful as an inhibitor of cyclooxygenase-2. EP 0863134; JP 1998251220 . |
| 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) | 25950 | 2-cyclopenten-1-one | 930-30-3 | C5H6O | 详情 | 详情 |
| (II) | 25951 | 2-bromo-2-cyclopenten-1-one | C5H5BrO | 详情 | 详情 | |
| (III) | 25952 | 3,5-difluorophenylboronic acid | 156545-07-2 | C6H5BF2O2 | 详情 | 详情 |
| (IV) | 25953 | 2-(3,5-difluorophenyl)-2-cyclopenten-1-one | C11H8F2O | 详情 | 详情 | |
| (V) | 18808 | [4-(methylsulfanyl)phenyl]lithium | C7H7LiS | 详情 | 详情 | |
| (VI) | 25954 | 2-(3,5-difluorophenyl)-1-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-ol | C18H16F2OS | 详情 | 详情 | |
| (VII) | 25955 | 2-(3,5-difluorophenyl)-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one | C18H14F2OS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The reaction of 4-(methylsulfanyl)acetophenone (I) with tosylhydrazine by means of PPTS in acetonitrile gives the corresponding hydrazone (II), which by reaction with isopropylmagnesium chloride in THF/toluene yields the vinylmagnesium derivative (III). This compound, without isolation is condensed with 3,5-difluorobenzaldehyde (IV) to afford the allyl alcohol (V), which is condensed with triethyl orthoacetate and saponified providing 5-(3,5-difluorophenyl)-4-[4-(methylsulfanyl)phenyl]-4-pentenoic acid (VI). The cyclization of (VI) with AlCl3 and (COCl)2 in dichloromethane gives the cyclopentenone (VII), which is finally oxidized with potassium peroxymonosulfate (Oxone) in hot acetone/water to afford the target sulfone.
| 【1】 Grabowski, E.J.J.; Zhaol, D.L.; Prasit, P.; Xu, F.; Ouimet, N.; Tillyer, R.D.; Black, C.; Chen, C.Y.; Reider, P.J.; Efficient syntheses of 2-(3 ',5 '-difluorophenyl)-3-(4 '-methylsulfonylphenyl)-cyclopent-2-enone, a potent COX-2 inhibitor. Tetrahedron 1999, 55, 19, 6001. |
| 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) | 19262 | 1-[4-(methylsulfanyl)phenyl]-1-ethanone；4'-Methylthioacetophenon；4’-(methylthio)acetophenone | 1778-09-2 | C9H10OS | 详情 | 详情 |
| (II) | 31619 | 4-methyl-N'-[(E)-1-[4-(methylsulfanyl)phenyl]ethylidene]benzenesulfonohydrazide | C16H18N2O2S2 | 详情 | 详情 | |
| (III) | 31620 | chloro[1-[4-(methylsulfanyl)phenyl]vinyl]magnesium | C9H9ClMgS | 详情 | 详情 | |
| (IV) | 31621 | 3,5-difluorobenzaldehyde | 32085-88-4 | C7H4F2O | 详情 | 详情 |
| (V) | 31622 | 1-(3,5-difluorophenyl)-2-[4-(methylsulfanyl)phenyl]-2-propen-1-ol | C16H14F2OS | 详情 | 详情 | |
| (VI) | 31623 | (Z)-5-(3,5-difluorophenyl)-4-[4-(methylsulfanyl)phenyl]-4-pentenoic acid | C18H16F2O2S | 详情 | 详情 | |
| (VII) | 25955 | 2-(3,5-difluorophenyl)-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one | C18H14F2OS | 详情 | 详情 |