tert-butyl (1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-4-pentenylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】62261

【品名】tert-butyl (1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-4-pentenylcarbamate

【CA登记号】

【分子式】C₂₂H₃₇NO₃Si

【分子量】391.62622

【元素组成】C 67.47% H 9.52% N 3.58% O 12.26% Si 7.17%

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：(XIV)

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：(XIV)

). The hydroxylation of the double bond of (XIV) by means of (Sia)2BH and H2O2 affords the pentanol (XV), which is treated with MsCl and TEA to provide the mesylate (XVI). The cyclization of (XVI) by means of t-BuOK in THF gives the piperidine (XVII), which is desilylated by means of TBAF to yield the piperidinol (XVIII). The oxidation of (XVIII) by means of DMP affords the piperidinone (XIX), which is treated with O-methylhydroxylamine and pyridine to provide the O-methyloxime (XX). The reduction of (XX) with BH3/THF gives the cis-disubstituted piperidine (XXI), which is submitted to a reductocondensation with 2-methoxybenzaldehyde (XXII) by means of NaBH3CN in methanol to yield the secondary amine (XXIII). Finally, the carbamate group of (XXIII) is cleaved by means of HCl in methanol to provide the target piperidine derivative

参考文献中间体

合成目标

【1】 Yamazaki, N.; et al.; Enantioselective synthesis of NK-1 receptor antagonists (+)-CP-99,994 and (+)-CP-122,721. Tetrahedron Lett 2002, 43, 44, 7979.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	62261	tert-butyl (1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-4-pentenylcarbamate		C₂₂H₃₇NO₃Si	详情	详情
(XV)	62262	tert-butyl (1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-1-phenylpentylcarbamate		C₂₂H₃₉NO₄Si	详情	详情
(XVI)	62263	(5S)-5-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-phenylpentyl methanesulfonate		C₂₃H₄₁NO₆SSi	详情	详情
(XVII)	62264	tert-butyl (2S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-phenyl-1-piperidinecarboxylate		C₂₂H₃₇NO₃Si	详情	详情
(XVIII)	62265	tert-butyl (2S)-3-hydroxy-2-phenyl-1-piperidinecarboxylate		C₁₆H₂₃NO₃	详情	详情
(XIX)	62266	tert-butyl (2S)-3-oxo-2-phenyl-1-piperidinecarboxylate		C₁₆H₂₁NO₃	详情	详情
(XX)	62267	tert-butyl (2S)-3-(methoxyimino)-2-phenyl-1-piperidinecarboxylate		C₁₇H₂₄N₂O₃	详情	详情
(XXI)	31756	tert-butyl (2S,3S)-3-amino-2-phenyl-1-piperidinecarboxylate		C₁₆H₂₄N₂O₂	详情	详情
(XXII)	12568	2-Methoxybenzaldehyde; o-Methoxybenzaldehyde	135-02-4	C₈H₈O₂	详情	详情
(XXIII)	31757	tert-butyl (2S,3S)-3-[(2-methoxybenzyl)amino]-2-phenyl-1-piperidinecarboxylate		C₂₄H₃₂N₂O₃	详情	详情

Extended Information