(2S)-2-(aminooxy)-2-phenyl-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】56143

【品名】(2S)-2-(aminooxy)-2-phenyl-1-ethanol

【CA登记号】

【分子式】C₈H₁₁NO₂

【分子量】153.18088

【元素组成】C 62.73% H 7.24% N 9.14% O 20.89%

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：(IV)

The reaction of 1(R)-phenylethane-1,2-diol (I) with N-hydroxyphthalimide (II) by means of DEAD and PPh3 gives the N-alcoxyphthalimide (III) with(S)-configuration. The hydrazinolysis of (III) with hydrazine hydrate affords the O-alkylhydroxylamine (IV), which is condensed with benzaldehyde (V) to provide the alkylated benzaldoxime (VI). The alkylation of the oxime (VI) with vinyl lithium (VII) in toluene gives the N, O dialkylated hydroxylamine (VIII), which is treated with Zn and AcOH to yield 1(R)-phenylallylamine (IX). The protection of the amine (IX) with Boc2O and NaOH affords the carbamate (X), which is oxidized at the vinyl double bond by means of OsO4 and NaIO4 to provide the acetaldehyde (XI). The reaction of aldehyde (XI) with allylmagnesium bromide (XII) in ethyl ether gives the aminoalcohol (XIII), which is protected with Tbdms-Cl and imidazole to yield the silyl ether (XIV).

参考文献中间体

合成目标

【1】 Yamazaki, N.; et al.; Nucleophilic addition of methyllithium to chiral oxime ethers: Asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue. Tetrahedron Lett 2001, 42, 30, 5029.

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)	56141	(R)-(-)-1-Phenyl-1,2-ethanediol; (R)-(-)-alpha,beta-Dihydroxyethylbenzene; (R)-(-)-Phenyl-1,2-ethanediol; (R)-(-)-Styrene glycol; (-)-Styrene glycol	16355-00-3	C₈H₁₀O₂	详情	详情
(II)	13505	N-Hydroxyphthalimide; 2-Hydroxy-1H-isoindole-1,3(2H)-dione	524-38-9	C₈H₅NO₃	详情	详情
(III)	56142	2-{[(1S)-2-hydroxy-1-phenylethyl]oxy}-1H-isoindole-1,3(2H)-dione		C₁₆H₁₃NO₄	详情	详情
(IV)	56143	(2S)-2-(aminooxy)-2-phenyl-1-ethanol		C₈H₁₁NO₂	详情	详情
(V)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(VI)	62256	benzaldehyde O-[(1S)-2-hydroxy-1-phenylethyl]oxime		C₁₅H₁₅NO₂	详情	详情
(VII)	42368	vinyllithium	917-57-7	C₂H₃Li	详情	详情
(VIII)	62257	(2S)-2-phenyl-2-({[(1R)-1-phenyl-2-propenyl]amino}oxy)-1-ethanol		C₁₇H₁₉NO₂	详情	详情
(IX)	62258	(1R)-1-phenyl-2-propenylamine; (1R)-1-phenyl-2-propen-1-amine		C₉H₁₁N	详情	详情
(X)	62259	tert-butyl (1R)-1-phenyl-2-propenylcarbamate		C₁₄H₁₉NO₂	详情	详情
(XI)	45428	tert-butyl (1S)-2-oxo-1-phenylethylcarbamate		C₁₃H₁₇NO₃	详情	详情
(XII)	61128			C₄H₈	详情	详情
(XIII)	62260	tert-butyl (1S)-2-hydroxy-1-phenyl-4-pentenylcarbamate		C₁₆H₂₃NO₃	详情	详情
(XIV)	62261	tert-butyl (1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-4-pentenylcarbamate		C₂₂H₃₇NO₃Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

A new procedure for the asymmetric synthesis of amine (III) was reported. Mitsunobu coupling of N-hydroxyphthalimide (V) with the chiral auxiliary (R)-phenylglycol (IV) yielded the (S)-alkoxyphthalimide (VI). Hydrazinolysis of (VI) provided the free alkoxyamine (VII), which was condensed with 3-methoxybenzaldehyde (VIII) to afford oxime (IX). Diastereoselective addition of methyllithium to the oxime ether (IX) led to the methyl adduct (X) as the major isomer. Then, reductive N-O bond cleavage to furnish amine (III) was carried out by using zinc-acetic acid or, with an improved yield, using molybdenum hexacarbonyl.

参考文献中间体

合成目标

【1】 Yamazaki, N.; et al.; Nucleophilic addition of methyllithium to chiral oxime ethers: Asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue. Tetrahedron Lett 2001, 42, 30, 5029.

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)	56140	(R)-1-(3-Methoxyphenyl)ethylamine; (R)-3-Methoxy-alpha-methylbenzylamine; (R)-m-Methoxy-alpha-methylbenzylamine	88196-70-7	C₉H₁₃NO	详情	详情
(IV)	56141	(R)-(-)-1-Phenyl-1,2-ethanediol; (R)-(-)-alpha,beta-Dihydroxyethylbenzene; (R)-(-)-Phenyl-1,2-ethanediol; (R)-(-)-Styrene glycol; (-)-Styrene glycol	16355-00-3	C₈H₁₀O₂	详情	详情
(V)	13505	N-Hydroxyphthalimide; 2-Hydroxy-1H-isoindole-1,3(2H)-dione	524-38-9	C₈H₅NO₃	详情	详情
(VI)	56142	2-{[(1S)-2-hydroxy-1-phenylethyl]oxy}-1H-isoindole-1,3(2H)-dione		C₁₆H₁₃NO₄	详情	详情
(VII)	56143	(2S)-2-(aminooxy)-2-phenyl-1-ethanol		C₈H₁₁NO₂	详情	详情
(VIII)	20589	3-methoxybenzaldehyde; m-Anisaldehyde	591-31-1	C₈H₈O₂	详情	详情
(IX)	56144	3-methoxybenzaldehyde O-[(1S)-2-hydroxy-1-phenylethyl]oxime		C₁₆H₁₇NO₃	详情	详情
(X)	56145	(2S)-2-({[(1R)-1-(3-methoxyphenyl)ethyl]amino}oxy)-2-phenyl-1-ethanol		C₁₇H₂₁NO₃	详情	详情

Extended Information