2,4,4-trimethyl-5,6-dihydro-4H-1,3-oxazine -Drug Synthesis Database

【结构式】

【分子编号】46630

【品名】2,4,4-trimethyl-5,6-dihydro-4H-1,3-oxazine

【CA登记号】

【分子式】C₇H₁₃NO

【分子量】127.18636

【元素组成】C 66.11% H 10.3% N 11.01% O 12.58%

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：(XXIII)

Chiral octadienoic aldehyde intermediate (XXV): The reaction of the silylated allyl bromide (XX) with CrCl2 in THF gives the Cr derivative (XXI), which is condensed with the chiral pentanoic aldehyde intermediate (XIX) to yield the secondary alcohol (XXII). Elimination of the Tms group of (XXII) by means of KH in THF affords the desired (Z)-diene (XXIII), which is desilylated by means of CSA in methanol/dichloromethane to provide the primary alcohol (XXIV). Finally this compound is oxidized by means of DMP in dichloromethane to furnish the target, chiral octadienoic aldehyde intermediate (XXV).

参考文献中间体

合成目标

【1】 Paterson, I.; Florence, G.J.; Gerlach, K.; Scott, J.P.; Sereinig, N.; A practical synthesis of (+)-discodermolide and analogues: Fragment union by complex aldol reactions. J Am Chem Soc 2001, 123, 39, 9535.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIX)	42628	(2R,3R,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal		C₂₁H₃₆O₄Si	详情	详情
(XX)	42629	(1-bromo-2-propenyl)(trimethyl)silane	94397-40-7	C₆H₁₃BrSi	详情	详情
(XXI)	62840	chloro[(E)-3-(trimethylsilyl)-2-propenyl]chromium		C₆H₁₃ClCrSi	详情	详情
(XXII)	62841	(3R,4S,5S,6R,7S)-8-{[tert-butyl(dimethyl)silyl]oxy}-6-[(4-methoxybenzyl)oxy]-5,7-dimethyl-3-(trimethylsilyl)-1-octen-4-ol		C₂₇H₅₀O₄Si₂	详情	详情
(XXIII)	46630	2,4,4-trimethyl-5,6-dihydro-4H-1,3-oxazine		C₇H₁₃NO	详情	详情
(XXIV)	42631	(2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadien-1-ol		C₁₈H₂₆O₃	详情	详情
(XXV)	42632	(2R,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienal		C₁₈H₂₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The cyclization of 3-methyl-2-buten-1-ol (I) with acetonitrile (II) gives 2,4,4-trimethyl-5,6-dihydro-4H-1,3-oxazine (III), which is hydrolyzed with NaOH to yield 3-amino-3-methyl-1-butanol (IV). The protection of the amino group of (IV) with (Boc)2O in isopropanol affords the carbamate (V), which is oxidized at the primary OH group with SO3/pyridine and TEA to provide the aldehyde (VI). The condensation of (VI) with triethyl phosphonoacetate (VII) by means of potassium tert-butoxide in hot toluene gives the desired hexenoic ester (intermediate 27230), which is hydrolyzed with NaOH in refluxing ethanol to yield the corresponding acid intermediate (intermediate 22191).

参考文献中间体

合成目标

【1】 Jessen, C.U.; et al.; Synthesis of N-protected 14C-labelled (2E)-5-amino-5-methylhex-2-enoic acid analogues. J Label Compd Radiopharm 2001, 44, 4, 265.

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)	37754	3-methyl-2-buten-1-ol	556-82-1	C₅H₁₀O	详情	详情
(II)	37210	acetonitrile	75-05-8	C₂H₃N	详情	详情
(III)	46630	2,4,4-trimethyl-5,6-dihydro-4H-1,3-oxazine		C₇H₁₃NO	详情	详情
(IV)	46631	3-amino-3-methyl-1-butanol		C₅H₁₃NO	详情	详情
(V)	22194	tert-butyl 3-hydroxy-1,1-dimethylpropylcarbamate		C₁₀H₂₁NO₃	详情	详情
(VI)	22195	tert-butyl 1,1-dimethyl-3-oxopropylcarbamate		C₁₀H₁₉NO₃	详情	详情
(VII)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(VIII)	27230	ethyl (E)-5-[(tert-butoxycarbonyl)amino]-5-methyl-2-hexenoate		C₁₄H₂₅NO₄	详情	详情
(IX)	22191	(E)-5-[(tert-butoxycarbonyl)amino]-5-methyl-2-hexenoic acid		C₁₂H₂₁NO₄	详情	详情

Extended Information