tert-butyl (2R,3R,5S,6S)-2,5-dimethyl-6-(2-oxoethyl)tetrahydro-2H-pyran-3-ylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】62147

【品名】tert-butyl (2R,3R,5S,6S)-2,5-dimethyl-6-(2-oxoethyl)tetrahydro-2H-pyran-3-ylcarbamate

【CA登记号】

【分子式】C₁₄H₂₅NO₄

【分子量】271.35684

【元素组成】C 61.97% H 9.29% N 5.16% O 23.58%

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：(X)

In a different synthetic strategy, the known Garner's aldehyde (I) is subjected to a Wittig reaction with phosphorane (II) to give the unsaturated ester (III), which is subsequently hydrogenated, producing (IV) as an inseparable mixture of diastereoisomers. Oxazolidine hydrolysis in (IV), followed by cyclization under acidic conditions leads to lactone (V). This is then converted to the thiolactone (VI) upon treatment with Lawesson's reagent in hot toluene. Condensation of thiolactone (VI) with the Wittig reagent (VII), followed by double bond isomerization in the presence of DBU furnishes the dihydropyran derivative (VIII). Stereoselective hydrogenation of the double bond of (VIII) with PtO2 gives rise to the desired all-cis isomer (IX). The methyl vester group of (IX) is then reduced to aldehyde (X) by means of DIBAL in cold toluene.

参考文献中间体

合成目标

【1】 Horigome, M.; Motoyoshi, H.; Watanabe, H.; Kitahara, T.; A synthesis of FR901464. Tetrahedron Lett 2001, 42, 46, 8207.

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)	62140	tert-butyl (4S,5R)-4-formyl-2,2,5-trimethyl-1,3-oxazolidine-3-carboxylate		C₁₂H₂₁NO₄	详情	详情
(II)	37071	ethyl 2-(triphenylphosphoranylidene)propanoate	5717-37-3	C₂₃H₂₃O₂P	详情	详情
(III)	62141	tert-butyl (4R,5R)-4-[(E)-3-ethoxy-2-methyl-3-oxo-1-propenyl]-2,2,5-trimethyl-1,3-oxazolidine-3-carboxylate		C₁₇H₂₉NO₅	详情	详情
(IV)	62142	tert-butyl (4R,5R)-4-(3-ethoxy-2-methyl-3-oxopropyl)-2,2,5-trimethyl-1,3-oxazolidine-3-carboxylate		C₁₇H₃₁NO₅	详情	详情
(V)	62143	tert-butyl (2R,3R)-2,5-dimethyl-6-oxotetrahydro-2H-pyran-3-ylcarbamate		C₁₂H₂₁NO₄	详情	详情
(VI)	62144	tert-butyl (2R,3R,5R)-2,5-dimethyl-6-thioxotetrahydro-2H-pyran-3-ylcarbamate		C₁₂H₂₁NO₃S	详情	详情
(VII)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(VIII)	62145	methyl 2-{(2R,3R)-3-[(tert-butoxycarbonyl)amino]-2,5-dimethyl-3,4-dihydro-2H-pyran-6-yl}acetate		C₁₅H₂₅NO₅	详情	详情
(IX)	62146	methyl 2-{(2S,3S,5R,6R)-5-[(tert-butoxycarbonyl)amino]-3,6-dimethyltetrahydro-2H-pyran-2-yl}acetate		C₁₅H₂₇NO₅	详情	详情
(X)	62147	tert-butyl (2R,3R,5S,6S)-2,5-dimethyl-6-(2-oxoethyl)tetrahydro-2H-pyran-3-ylcarbamate		C₁₄H₂₅NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Wittig reaction of aldehyde (X) with phosphorane (II) produces the unsaturated ester (XI), which is further reduced to the allylic alcohol (XII) with DIBAL in toluene. Treatment of (XII) with CBr4 and PPh3 leads to allyl bromide (XIII). This is then condensed with sodium p-toluenesulfinate (XIV), providing sulfone (XV). Subsequent acidic Boc group cleavage gives amine (XVI).

参考文献中间体

合成目标

【1】 Horigome, M.; Motoyoshi, H.; Watanabe, H.; Kitahara, T.; A synthesis of FR901464. Tetrahedron Lett 2001, 42, 46, 8207.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	37071	ethyl 2-(triphenylphosphoranylidene)propanoate	5717-37-3	C₂₃H₂₃O₂P	详情	详情
(X)	62147	tert-butyl (2R,3R,5S,6S)-2,5-dimethyl-6-(2-oxoethyl)tetrahydro-2H-pyran-3-ylcarbamate		C₁₄H₂₅NO₄	详情	详情
(XI)	62148	ethyl (E)-4-{(2S,3S,5R,6R)-5-[(tert-butoxycarbonyl)amino]-3,6-dimethyltetrahydro-2H-pyran-2-yl}-2-methyl-2-butenoate		C₁₉H₃₃NO₅	详情	详情
(XII)	62149	tert-butyl (2R,3R,5S,6S)-6-[(E)-4-hydroxy-3-methyl-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran-3-ylcarbamate		C₁₇H₃₁NO₄	详情	详情
(XIII)	62150	tert-butyl (2R,3R,5S,6S)-6-[(E)-4-bromo-3-methyl-2-butenyl]-2,5-dimethyltetrahydro-2H-pyran-3-ylcarbamate		C₁₇H₃₀BrNO₃	详情	详情
(XIV)	62151	4-methylbenzenesulfinate		C₇H₇O₂S	详情	详情
(XV)	62152	tert-butyl (2R,3R,5S,6S)-2,5-dimethyl-6-{(E)-3-methyl-4-[(4-methylphenyl)sulfonyl]-2-butenyl}tetrahydro-2H-pyran-3-ylcarbamate		C₂₄H₃₇NO₅S	详情	详情
(XVI)	62153	(2R,3R,5S,6S)-2,5-dimethyl-6-{(E)-3-methyl-4-[(4-methylphenyl)sulfonyl]-2-butenyl}tetrahydro-2H-pyran-3-amine; (2R,3R,5S,6S)-2,5-dimethyl-6-{(E)-3-methyl-4-[(4-methylphenyl)sulfonyl]-2-butenyl}tetrahydro-2H-pyran-3-ylamine		C₁₉H₂₉NO₃S	详情	详情

Extended Information