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【结 构 式】

【分子编号】60491

【品名】tert-butyl (3R)-3-{[tert-butyl(diphenyl)silyl]oxy}-6-[(methylsulfonyl)oxy]-8-oxo-1-azaspiro[4.5]decane-1-carboxylate

【CA登记号】

【 分 子 式 】C31H43NO7SSi

【 分 子 量 】601.83646

【元素组成】C 61.87% H 7.2% N 2.33% O 18.61% S 5.33% Si 4.67%

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:(VIII)

The alkylation of the protected hydroxyproline (I) with 4-iodo-1-butene (II) by means of LDA in THF gives the 2-alkylproline (III), which is reduced with DIBAL in toluene to yield the carbinol (IV). The oxidation of (IV) by means of TPAP and NMO in dichloromethane affords the carbaldehyde (V), which is oxidated at its terminal vinyl group by means of PdCl2, CuCl2 and O2 in aqueous DMF to provide the methyl ketone (VI). The cyclization of (VI) by means of KOH in ethanol furnishes the cyclic aldol (VII), which is treated with Ms-Cl and TEA to give the mesylate (VIII). The elimination reaction of (VIII) over chromatographic silicagel yields enone (IX), which is hydrogenated with H2 over Pd/C in benzene to afford the spiranic ketone (X). The reaction of (X) with ethyleneglycol and Ts-OH in refluxing benzene provides the ethylene ketal (XI), which is desilylated by means of TBAF in THF to gives the alcohol (XII). The reaction of (XII) with DPPA, DEAD and PPh3 in THF yields the azide (XIII), which is subjected to removal of the Boc protecting group by means of TFA affording unprotected spiro pyrrolidine derivative (XIV). Alkylation of (XIV) with ethyl bromoacetate (XV) by means of K2CO3 in acetonitrile provides the ester (XVI), which is reduced at the azido group by means of H2 over Pd/C in methanol to give the aminoester (XVII). The hydrolysis of the ester group of (XVII) with LiOH in water yields the spiranic aminoacid (XVIII), which is cyclized by means of DPPA and TEA in DMF to afford the tetracyclic amide (XIX). Finally this compound is methylated by means of methyl iodide and NaH in THF to provide the target tetracyclic intermediate (XX) (see scheme no.18599903a, intermediate (XV)).

1 Nagumo, S.; et al.; Synthesis of (-)-TAN1251A using 4-hydroxy-L-proline as a chiral source. Tetrahedron 2002, 58, 49, 9871.
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) 60484 1-(tert-butyl) 2-methyl (2S,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-1,2-pyrrolidinedicarboxylate C27H37NO5Si 详情 详情
(II) 60485 4-iodo-1-butene C4H7I 详情 详情
(III) 60486 1-(tert-butyl) 2-methyl (4R)-2-(3-butenyl)-4-{[tert-butyl(diphenyl)silyl]oxy}-1,2-pyrrolidinedicarboxylate C31H43NO5Si 详情 详情
(IV) 60487 tert-butyl (4R)-2-(3-butenyl)-4-{[tert-butyl(diphenyl)silyl]oxy}-2-(hydroxymethyl)-1-pyrrolidinecarboxylate C30H43NO4Si 详情 详情
(V) 60488 tert-butyl (4R)-2-(3-butenyl)-4-{[tert-butyl(diphenyl)silyl]oxy}-2-formyl-1-pyrrolidinecarboxylate C30H41NO4Si 详情 详情
(VI) 60489 tert-butyl (4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-2-formyl-2-(3-oxobutyl)-1-pyrrolidinecarboxylate C30H41NO5Si 详情 详情
(VII) 60490 tert-butyl (3R)-3-{[tert-butyl(diphenyl)silyl]oxy}-6-hydroxy-8-oxo-1-azaspiro[4.5]decane-1-carboxylate C30H41NO5Si 详情 详情
(VIII) 60491 tert-butyl (3R)-3-{[tert-butyl(diphenyl)silyl]oxy}-6-[(methylsulfonyl)oxy]-8-oxo-1-azaspiro[4.5]decane-1-carboxylate C31H43NO7SSi 详情 详情
(IX) 60492 tert-butyl (3R)-3-{[tert-butyl(diphenyl)silyl]oxy}-8-oxo-1-azaspiro[4.5]dec-6-ene-1-carboxylate C30H39NO4Si 详情 详情
(X) 60493 tert-butyl (3R)-3-{[tert-butyl(diphenyl)silyl]oxy}-8-oxo-1-azaspiro[4.5]decane-1-carboxylate C30H41NO4Si 详情 详情
(XI) 60494 tert-butyl (11R)-11-{[tert-butyl(diphenyl)silyl]oxy}-1,4-dioxa-9-azadispiro[4.2.4.2]tetradecane-9-carboxylate C32H45NO5Si 详情 详情
(XII) 60495 tert-butyl (11R)-11-hydroxy-1,4-dioxa-9-azadispiro[4.2.4.2]tetradecane-9-carboxylate C16H27NO5 详情 详情
(XIII) 60496 tert-butyl (11S)-11-azido-1,4-dioxa-9-azadispiro[4.2.4.2]tetradecane-9-carboxylate C16H26N4O4 详情 详情
(XIV) 60497 (11S)-1,4-dioxa-9-azadispiro[4.2.4.2]tetradec-11-yl azide; (11S)-11-azido-1,4-dioxa-9-azadispiro[4.2.4.2]tetradecane C11H18N4O2 详情 详情
(XV) 12309 methyl 2-bromoacetate; methyl bromoacetate 96-32-2 C3H5BrO2 详情 详情
(XVI) 60498   C14H22N4O4 详情 详情
(XVII) 60499   C14H24N2O4 详情 详情
(XVIII) 60648 2-[(11S)-11-amino-1,4-dioxa-9-azadispiro[4.2.4.2]tetradec-9-yl]acetic acid C13H22N2O4 详情 详情
(XIX) 60649   C13H20N2O3 详情 详情
(XX) 48806   C14H22N2O3 详情 详情
Extended Information