tert-butyl (2R)-2-vinyl-1-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】26737

【品名】tert-butyl (2R)-2-vinyl-1-piperidinecarboxylate

【CA登记号】

【分子式】C₁₂H₂₁NO₂

【分子量】211.30428

【元素组成】C 68.21% H 10.02% N 6.63% O 15.14%

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 acylation of 3-hydroxypiperidine with tosyl chloride followed by oxidation of the OH group with CrO3 and H2SO4 gives 1-tosylpiperidine-3-one (II), which is converted into the enol triflate (III) by reaction with LHMDS and PhN(SO2CF3)2 in THF. The condensation of (III) with 1-(tert-butoxycarbonyl)-2-vinylpiperidine (IV) by means of Pd(OAc)2 affords the diene (V), which is selectively deprotected with NaOH in methanol to afford the piperidine (VI). The condensation of (VI) with silylated methyl propenoate (VII) by means of triethylamine in dichloromethane gives the nonisolated intermediate (VIII) that cyclizes to the tetracyclic compound (IX) (as major isomer). The reaction of (IX) with HF and pyridine in refluxing dichloromethane affords the silylated tetracyclic ketone (X) (as major isomer), which is desilylated with KF, KHCO3 and H2O2 in refluxing methanol/THF providing the tetracyclic hydroxyketone (XI) (as major isomer), separated by column chromatography. Elimination of the OH group of (XI) with C6F5OC(S)-Cl, Bu3SnH and AIBN in refluxing benzdene yields the tetracyclic ketone (XII), which is finally reduced with LiAlH4 in THF.

参考文献中间体

合成目标

【1】 Brosius, A.D.; et al.; Total synthesis of (+)-aloperine. Use of a nitrogen-bound silicon tether in a intramolecular diels - Alder reaction. J Am Chem Soc 1999, 121, 4, 700.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	17573	N-Phenyltrifluoromethanesulfonimide; Trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyl]methanesulfonamide	37595-74-7	C₈H₅F₆NO₄S₂	详情	详情
(I)	24255	3-piperidinol	6859-99-0	C₅H₁₁NO	详情	详情
(II)	26735	1-(methylsulfonyl)-3-piperidinone		C₆H₁₁NO₃S	详情	详情
(III)	26736	1-(methylsulfonyl)-1,4,5,6-tetrahydro-3-pyridinyl trifluoromethanesulfonate		C₇H₁₀F₃NO₅S₂	详情	详情
(IV)	26737	tert-butyl (2R)-2-vinyl-1-piperidinecarboxylate		C₁₂H₂₁NO₂	详情	详情
(V)	26738	tert-butyl (2R)-2-[(E)-2-[1-(methylsulfonyl)-1,4,5,6-tetrahydro-3-pyridinyl]ethenyl]-1-piperidinecarboxylate		C₁₈H₃₀N₂O₄S	详情	详情
(VI)	26739	1-(methylsulfonyl)-5-[(E)-2-[(2R)piperidinyl]ethenyl]-1,2,3,4-tetrahydropyridine		C₁₃H₂₂N₂O₂S	详情	详情
(VII)	26750	methyl (E)-3-(dimethyl[[(trifluoromethyl)sulfonyl]oxy]silyl)-2-propenoate		C₇H₁₁F₃O₅SSi	详情	详情
(VIII)	26741	methyl (E)-3-[dimethyl((2R)-2-[(E)-2-[1-(methylsulfonyl)-1,4,5,6-tetrahydro-3-pyridinyl]ethenyl]piperidinyl)silyl]-2-propenoate		C₁₉H₃₂N₂O₄SSi	详情	详情
(IX)	26742	methyl (5aR,5bR,11aR,12S,12aS)-11,11-dimethyl-1-(methylsulfonyl)-1,2,3,4,5a,5b,6,7,8,9,11,11a,12,12a-tetradecahydropyrido[2',1':5,1][1,2]azasilolo[4,3-g]quinoline-12-carboxylate		C₁₉H₃₂N₂O₄SSi	详情	详情
(X)	26743	(1R,2S,9S,10R,17R)-17-[fluoro(dimethyl)silyl]-3-(methylsulfonyl)-3,15-diazatetracyclo[7.7.1.0(2,7).0(10,15)]heptadec-7-en-16-one		C₁₈H₂₉FN₂O₃SSi	详情	详情
(XI)	26744	(1R,2S,9R,10R,17R)-17-hydroxy-3-(methylsulfonyl)-3,15-diazatetracyclo[7.7.1.0(2,7).0(10,15)]heptadec-7-en-16-one		C₁₆H₂₄N₂O₄S	详情	详情
(XII)	26745	(1S,2S,9S,10R)-3-(methylsulfonyl)-3,15-diazatetracyclo[7.7.1.0(2,7).0(10,15)]heptadec-7-en-16-one		C₁₆H₂₄N₂O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Vinylpiperidine (IV): The reduction of (R)-piperidine-2-carboxylic acid (XIII) with BH3-THF gives the carbinol (XIV), which is protected at the NH group with tert-butoxycarbonyl anhydride yielding the N-protected carbinol (XV). The Swern oxidation of (XV) affords the corresponding aldehyde (XVI), which is finally condensed with trimethylphenylphosphonium bromide and potassium hexamethyldisylazane (KHMDS) in THF to provide the target intermediate (IV).

参考文献中间体

合成目标

【1】 Brosius, A.D.; et al.; Total synthesis of (+)-aloperine. Use of a nitrogen-bound silicon tether in a intramolecular diels - Alder reaction. J Am Chem Soc 1999, 121, 4, 700.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	26737	tert-butyl (2R)-2-vinyl-1-piperidinecarboxylate	C₁₂H₂₁NO₂	详情	详情
(XIII)	26751	(2R)-2-piperidinecarboxylic acid	C₆H₁₁NO₂	详情	详情
(XIV)	26746	(2R)-piperidinylmethanol	C₆H₁₃NO	详情	详情
(XV)	26747	tert-butyl (2R)-2-(hydroxymethyl)-1-piperidinecarboxylate	C₁₁H₂₁NO₃	详情	详情
(XVI)	26748	tert-butyl (2R)-2-formyl-1-piperidinecarboxylate	C₁₁H₁₉NO₃	详情	详情

Extended Information