(1R,2S)-(-)-2-Amino-1,2-diphenylethanol; (1S,2R)-2-amino-1,2-diphenyl-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】15141

【品名】(1R,2S)-(-)-2-Amino-1,2-diphenylethanol; (1S,2R)-2-amino-1,2-diphenyl-1-ethanol

【CA登记号】23190-16-1

【分子式】C₁₄H₁₅NO

【分子量】213.27924

【元素组成】C 78.84% H 7.09% N 6.57% O 7.5%

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：(XVII)

The chiral intermediate (1R,2S)-N-(tert-butoxycarbonyl)-2-fluorocyclopropylamine (III) can also be obtained as follows: 2) The cyclization of (1S,2R)-2-amino-1,2-diphenylethanol (XVII) with trichloromethyl chloroformate and triethylamine in dichloromethane gives (4R,5S)-4,5-diphenyloxazolidin-2-one (XVIII), which is treated with 1,1-dimethoxyethane and an acid catalyst, yielding the 1-methoxyethyl derivative (XIX). The heat treatment (150 C) of (XIX) affords the corresponding vinyl derivative (XX), which is cyclized with fluorodiiodomethane and diethyl zinc (a fluorocarbenoid compound) in a preferentially cis-way to afford the cyclopropyl-oxazolidinone (XXI), purified by column chromatography. The hydrogenolysis of (XXI) with H2 over Pd/C in acetic acid gives (1R,2S)-2-fluorocyclopropylamine (XXII), which is finally converted into (III) by reaction with tert-butoxycarbonyl anhydride and triethylamine in THF.

参考文献中间体

合成目标

【1】 Castaner, J.; Graul, A.; Prous, J.; DU-6859. Drugs Fut 1994, 19, 9, 827.
【2】 Tamura, O.; Hashimoto, M.; Kobayashi, Y.; Katoh, T.; Nakatani, K.; Kamada, M.; Hayakawa, I.; Akiba, T.; Terashima, S.; Asymmetric synthesis of (1R,2S)-2-fluorocyclopropylamine, the key intermediate of the new generation of quinolonecarboxylic acid, DU-6859. Tetrahedron Lett 1992, 33, 24, 3487-90.

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)	15127	tert-butyl N-[(1R,2S)-2-fluorocyclopropyl]carbamate	127199-16-0	C₈H₁₄FNO₂	详情	详情
(XVII)	15141	(1R,2S)-(-)-2-Amino-1,2-diphenylethanol; (1S,2R)-2-amino-1,2-diphenyl-1-ethanol	23190-16-1	C₁₄H₁₅NO	详情	详情
(XVIII)	15142	(4R,5S)-4,5-Diphenyl-1,3-oxazolan-2-one; (4S,5R)-(-)-4,5-Diphenyl-2-oxazolidinone	86286-50-2	C₁₅H₁₃NO₂	详情	详情
(XIX)	15143	(4R,5S)-3-[(1R)-1-Methoxyethyl]-4,5-diphenyl-1,3-oxazolan-2-one		C₁₈H₁₉NO₃	详情	详情
(XX)	15144	(4R,5S)-4,5-diphenyl-3-vinyl-1,3-oxazolan-2-one		C₁₇H₁₅NO₂	详情	详情
(XXI)	15145	(4R,5S)-3-[(1R,2S)-2-fluorocyclopropyl]-4,5-diphenyl-1,3-oxazolan-2-one		C₁₈H₁₆FNO₂	详情	详情
(XXII)	15146	(1R,2S)-2-Fluorocyclopropanamine; (1R,2S)-2-Fluorocyclopropylamine		C₃H₆FN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Chiral resolution of protected dl-thiopropionic acid derivative (I) is performed by first condensation with (1R,2S)-(-)-2-amino-1,2-diphenyl ethanol in acetonitrile followed by diastereomer separation and finally hydrolysis of the optically active salt to afford the desired stereoisomer (S)-(II). Activation of (S)-(II) with oxalyl chloride in dichloromethane and subsequent coupling to L-isoglutamine derivative (III) in CH2Cl2 in the presence of pyridine provides amide (S)-(IV), which is finally converted into the target product by alkaline hydrolysis with LiOH in THF.

参考文献中间体

合成目标

【1】 Katsube, N.; Nakai, H.; Nagao, Y.; Sakai, Y.; Senokuchi, K.; Kawamura, M.; New orally active enkephalinase inhibitors: Their synthesis, biological activity, and analgesic properties. Bioorg Med Chem 1998, 6, 4, 441.

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)	48898	3-(benzoylsulfanyl)-2-benzylpropionic acid		C₁₇H₁₆O₃S	详情	详情
(II)	15141	(1R,2S)-(-)-2-Amino-1,2-diphenylethanol; (1S,2R)-2-amino-1,2-diphenyl-1-ethanol	23190-16-1	C₁₄H₁₅NO	详情	详情
(III)	48899	(2S)-3-(benzoylsulfanyl)-2-benzylpropionic acid		C₁₇H₁₆O₃S	详情	详情
(IV)	48900	benzyl (4S)-4-amino-5-anilino-5-oxopentanoate		C₁₈H₂₀N₂O₃	详情	详情
(V)	48901	benzyl (4S)-5-anilino-4-[[(2S)-3-(benzoylsulfanyl)-2-benzylpropanoyl]amino]-5-oxopentanoate		C₃₅H₃₄N₂O₅S	详情	详情

Extended Information