methyl (2R)-1-methyl-2-pyrrolidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】31538

【品名】methyl (2R)-1-methyl-2-pyrrolidinecarboxylate

【CA登记号】

【分子式】C₇H₁₃NO₂

【分子量】143.18576

【元素组成】C 58.72% H 9.15% N 9.78% O 22.35%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VII)

Alternatively, 5-methoxyindole (III) was N-silylated employing tert-butyldimethylsilyl chloride and n-BuLi, and the resulting silyl derivative (V) was brominated with N-bromosuccinimide at -78 C to afford the 3-bromoindole (VI). After lithium-bromine exchange in (VI) with n-BuLi at -78 C, the 3-lithio compound was condensed with N-methyl-D-proline methyl ester (VII) to give the indolyl ketone (VIII). The ketone function of (VIII) was finally reduced employing LiAlH4 in boiling THF.

参考文献中间体

合成目标

【1】 Qandil, A.M.; Marona-Lewicka, D.; Gerasimov, M.; Kurrasch-Orbaugh, D.M.; Nichols, D.E.; Further studies on oxygenated tryptamines with LSD-like activity incorporating a chiral pyrrolidine moiety into the side chain. J Med Chem 1999, 42, 20, 4257.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	25902	1H-Indol-5-yl methyl ether; 5-Methoxy-1H-indole; 5-Methoxyindole	1006-94-6	C₉H₉NO	详情	详情
(V)	31541	1-[tert-butyl(dimethyl)silyl]-1H-indol-5-yl methyl ether; 1-[tert-butyl(dimethyl)silyl]-5-methoxy-1H-indole		C₁₅H₂₃NOSi	详情	详情
(VI)	31542	3-bromo-1-[tert-butyl(dimethyl)silyl]-5-methoxy-1H-indole; 3-bromo-1-[tert-butyl(dimethyl)silyl]-1H-indol-5-yl methyl ether		C₁₅H₂₂BrNOSi	详情	详情
(VII)	31538	methyl (2R)-1-methyl-2-pyrrolidinecarboxylate		C₇H₁₃NO₂	详情	详情
(VIII)	31543	(5-methoxy-1H-indol-3-yl)[(2R)-1-methylpyrrolidinyl]methanone		C₁₅H₁₈N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Silylation of 4-benzyloxyindole (I) employing tert-butyldimethylsilyl chloride and NaH gave the N-silyl derivative (II), which was brominated with N-bromosuccinimide at -78 C to afford the 3-bromoindole (III). After lithium-bromine exchange with n-BuLi at -78 C, the 3-lithio compound was condensed with N-methyl-D-proline methyl ester (IV) to give the indolyl ketone (V). The ketone function of (V) was finally reduced employing LiAlH4 in boiling dioxan, with concomitant cleavage of the benzyl ether to furnish the title compound.

参考文献中间体

合成目标

【1】 Qandil, A.M.; Marona-Lewicka, D.; Gerasimov, M.; Kurrasch-Orbaugh, D.M.; Nichols, D.E.; Further studies on oxygenated tryptamines with LSD-like activity incorporating a chiral pyrrolidine moiety into the side chain. J Med Chem 1999, 42, 20, 4257.

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)	31535	4-Benzyloxyindole; 4-(benzyloxy)-1H-indole; benzyl 1H-indol-4-yl ether	20289-26-3	C₁₅H₁₃NO	详情	详情
(II)	31536	4-(benzyloxy)-1-[tert-butyl(dimethyl)silyl]-1H-indole; benzyl 1-[tert-butyl(dimethyl)silyl]-1H-indol-4-yl ether		C₂₁H₂₇NOSi	详情	详情
(III)	31537	benzyl 3-bromo-1-[tert-butyl(dimethyl)silyl]-1H-indol-4-yl ether; 4-(benzyloxy)-3-bromo-1-[tert-butyl(dimethyl)silyl]-1H-indole		C₂₁H₂₆BrNOSi	详情	详情
(IV)	31538	methyl (2R)-1-methyl-2-pyrrolidinecarboxylate		C₇H₁₃NO₂	详情	详情
(V)	31539	[4-(benzyloxy)-1H-indol-3-yl][(2R)-1-methylpyrrolidinyl]methanone		C₂₁H₂₂N₂O₂	详情	详情

Extended Information