【结 构 式】 |
【分子编号】55511 【品名】(E)-1-(2-bromo-4-methylphenyl)-3-phenyl-2-propen-1-one 【CA登记号】 |
【 分 子 式 】C16H13BrO 【 分 子 量 】301.18262 【元素组成】C 63.81% H 4.35% Br 26.53% O 5.31% |
合成路线1
该中间体在本合成路线中的序号:(III)The condensation of 2'-bromo-4'-methylacetophenone (I) with benzaldehyde (II) by means of NaOMe in methanol gives the propenone (III), which is cyclized by means of PdCl2, PPh3 and K2CO3 in DMF, yielding 5-methyl-3-phenyl-1-indenone (IV). The enantioselective reduction of (IV) by means of borane/Me2S complex and (R)-3,3-diphenyl-1-methyltetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole [(R)-MeCBS] as chiral catalyst in THF affords 5-methyl-3(S)-phenylindan-1-ol (V), which is oxidized with 1,4-diazabicyclo[2,2,2]octane (DABCO) in refluxing THF/TEA to provide the corresponding indanone (VI). The oxidation of (VI) with MCPBA in dichloromethane gives 6-methyl-4(S)-phenyl-3,4-dihydro-2H-1-benzopyran-2-one (VII), which is reduced with DIBAL in toluene to yield 6-methyl-4(S)-phenyl-3,4-dihydro-2H-1-benzopyran-2-ol (VIII). Finally, this compound is reductocondensed with diisopropylamine (IX) by means of H2 over Pd/C in methanol to afford the target compound.
【1】 Andersson, P.G.; Hedberg, C. (Pharmacia & Upjohn AB); Process of preparing tolterodine and analogues there of as well as intermediates prepared in the process. WO 0149649 . |
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) | 55510 | 1-(2-bromo-4-methylphenyl)-1-ethanone | C9H9BrO | 详情 | 详情 | |
(II) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
(III) | 55511 | (E)-1-(2-bromo-4-methylphenyl)-3-phenyl-2-propen-1-one | C16H13BrO | 详情 | 详情 | |
(IV) | 55512 | 5-methyl-3-phenyl-1H-inden-1-one | C16H12O | 详情 | 详情 | |
(V) | 55513 | (3R)-5-methyl-3-phenyl-2,3-dihydro-1H-inden-1-ol | C16H16O | 详情 | 详情 | |
(VI) | 55514 | (3R)-5-methyl-3-phenyl-2,3-dihydro-1H-inden-1-one | C16H14O | 详情 | 详情 | |
(VII) | 55515 | (4R)-6-methyl-4-phenyl-3,4-dihydro-2H-chromen-2-one | C16H14O2 | 详情 | 详情 | |
(VIII) | 55516 | (4R)-6-methyl-4-phenyl-3,4-dihydro-2H-chromen-2-ol | C16H16O2 | 详情 | 详情 | |
(IX) | 13565 | N-Isopropyl-2-propanamine; Bis(isopropyl)amine; N,N-Diisopropylamine | 108-18-9 | C6H15N | 详情 | 详情 |