【结 构 式】 |
【分子编号】33132 【品名】(3R,7aR)-3-(tert-butyl)-7a-[2-methoxy-6-(methoxymethoxy)benzyl]tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-1-one 【CA登记号】 |
【 分 子 式 】C20H29NO5 【 分 子 量 】363.454 【元素组成】C 66.09% H 8.04% N 3.85% O 22.01% |
合成路线1
该中间体在本合成路线中的序号:(XIII)The chiral intermediate (V) can also be obtained as follows: The cyclization of L-proline (VII) with pivalaldehyde (VIII) by means of LDA gives the pyrrolooxazolidinone (IX), which is condensed with the benzaldehyde (X) by means of LDA in THF yielding the alcohol (XI). The reaction of (XI) with I2, PPh3 and imidazole affords the corresponding iodide (XII), which is deiodinated with SmI2 to the intermediate (XIII). The hydrolysis of the oxazolidinone ring of (XIII) with refluxing methanol/water gives the pyrrolidine-carboxylic acid (XIV), which is reduced with BH3 in THF yielding the carbinol (XV). The protection of the NH group of (XV) with Boc2O in THF affords the carbamate (XVI), which is treated with trimethylsilyl bromide in dichloromethane to provide he diol (XVII). The cyclization of (XVII) by means of triphenylphosphine and diethyl azodicarboxylate (DEAD) in ether gives the chiral protected spiro-benzopyran (XVIII), which is finally deprotected with TFA in dichloromethane to afford the desired chiral intermediate (V).
【1】 Usse, S.; et al.; Synthesis of a chiral spiranic aminochroan derivative from L-proline. J Org Chem 2000, 65, 3, 914. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(V) | 33127 | (R)-5-Methoxy-3,4-dihydro-2H-spiro[1-benzopyran-3,2'-pyrrolidine] | C13H17NO2 | 详情 | 详情 | |
(VII) | 16731 | L-proline | 147-85-3 | C5H9NO2 | 详情 | 详情 |
(VIII) | 19797 | Trimethylacetaldehyde; pivalaldehyde; 2,2-Dimethylpropionaldehyde; 2,2-Dimethylpropanal | 630-19-3 | C5H10O | 详情 | 详情 |
(IX) | 33128 | (3R,7aS)-3-(tert-butyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-1-one | C10H17NO2 | 详情 | 详情 | |
(X) | 33129 | 2-methoxy-6-(methoxymethoxy)benzaldehyde | C10H12O4 | 详情 | 详情 | |
(XI) | 33130 | (3R,7aR)-3-(tert-butyl)-7a-[(R)-hydroxy[2-methoxy-6-(methoxymethoxy)phenyl]methyl]tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-1-one | C20H29NO6 | 详情 | 详情 | |
(XII) | 33131 | (3R,7aS)-3-(tert-butyl)-7a-[(R)-iodo[2-methoxy-6-(methoxymethoxy)phenyl]methyl]tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-1-one | C20H28INO5 | 详情 | 详情 | |
(XIII) | 33132 | (3R,7aR)-3-(tert-butyl)-7a-[2-methoxy-6-(methoxymethoxy)benzyl]tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-1-one | C20H29NO5 | 详情 | 详情 | |
(XIV) | 33133 | (2R)-2-[2-methoxy-6-(methoxymethoxy)benzyl]-2-pyrrolidinecarboxylic acid | C15H21NO5 | 详情 | 详情 | |
(XV) | 33134 | [(2R)-2-[2-methoxy-6-(methoxymethoxy)benzyl]pyrrolidinyl]methanol | C15H23NO4 | 详情 | 详情 | |
(XVI) | 33135 | tert-butyl (2R)-2-(hydroxymethyl)-2-[2-methoxy-6-(methoxymethoxy)benzyl]-1-pyrrolidinecarboxylate | C20H31NO6 | 详情 | 详情 | |
(XVII) | 33136 | tert-butyl (2R)-2-(2-hydroxy-6-methoxybenzyl)-2-(hydroxymethyl)-1-pyrrolidinecarboxylate | C18H27NO5 | 详情 | 详情 | |
(XVIII) | 33137 | (R)-5-Methoxy-3,4-dihydro-2H-spiro[1-benzopyran-3,2'-pyrrolidine]-1'-carboxylic acid tert-buytyl ester | C18H25NO4 | 详情 | 详情 |