(3R,4S)-4-[(tert-butoxycarbonyl)amino]-3-[[tert-butyl(dimethyl)silyl]oxy]-5-phenylpentanoic acid -Drug Synthesis Database

【结构式】

【分子编号】50336

【品名】(3R,4S)-4-[(tert-butoxycarbonyl)amino]-3-[[tert-butyl(dimethyl)silyl]oxy]-5-phenylpentanoic acid

【CA登记号】

【分子式】C₂₂H₃₇NO₅Si

【分子量】423.62502

【元素组成】C 62.38% H 8.8% N 3.31% O 18.88% Si 6.63%

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：(V)

The intermediate (3R,4S)-4-[N-(tert-butoxycarbonyl)-N-methylamino]-5-phenyl-3-(tert-butyldimethylsilyloxy)pentanoic acid (VII) has been obtained as follows: The condensation of N-(tert-butoxycarbonyl)-L-phenylalanine (I) with the Mg salt of malonic acid monoethyl ester (II) by means of CDI gives the beta-ketoester (III), which is reduced with NaBH4 to yield (3R,4S)-4-(tert-butoxycarbonylamino)-3-hydroxy-5-phenylpentanoic acid ethyl ester (IV). The protection of the OH group of (IV) with Tbdms-Cl and imidazole in DMF affords the silylated ester (V), which is hydrolyzed with NaOH to provide the corresponding carboxylic acid (VI). Finally, this compound is N-methylated by means of Me-I and NaH in THF to obtain the target intermediate (VII).

参考文献中间体

合成目标

【1】 Rich, D.H.; Maibaum, J.; A facile synthesis of statine and analogues by reduction of beta-keto esters derived from Boc-protected amino acids. HPLC analyses of their enantiomeric purity. J Org Chem 1988, 53, 4, 869.
【2】 Ohmori, K.; et al.; Synthetic study on hapalosin, a cyclic depsipeptide possessing multidrug resistance reversing activities. Tetrahedron Lett 1996, 37, 20, 3467.
【3】 Parkes, K.E.B.; Bushnell, D.J.; Crackett, P.H.; et al.; Studies toward the large-scale synthesis of the HIV proteinase inhibitor Ro 31-8959. J Org Chem 1994, 59, 13, 3656.

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)	12874	(2R)-2-[(tert-Butoxycarbonyl)amino]-3-phenylpropionic acid; N-alpha-t-BOC-L-Phenylalanine	13734-34-4	C₁₄H₁₉NO₄	详情	详情
(II)	14507	Malonic acid monoethyl ester magnesium salt		C₅H₆MgO₄	详情	详情
(III)	12876	ethyl (4S)-4-[(tert-butoxycarbonyl)amino]-3-oxo-5-phenylpentanoate		C₁₈H₂₅NO₅	详情	详情
(IV)	50335	ethyl (3R,4S)-4-[(tert-butoxycarbonyl)amino]-3-[[tert-butyl(dimethyl)silyl]oxy]-5-phenylpentanoate		C₂₄H₄₁NO₅Si	详情	详情
(V)	50336	(3R,4S)-4-[(tert-butoxycarbonyl)amino]-3-[[tert-butyl(dimethyl)silyl]oxy]-5-phenylpentanoic acid		C₂₂H₃₇NO₅Si	详情	详情
(VI)	50337	(3R,4S)-4-[(tert-butoxycarbonyl)(methyl)amino]-3-[[tert-butyl(dimethyl)silyl]oxy]-5-phenylpentanoic acid		C₂₃H₃₉NO₅Si	详情	详情

Extended Information