methyl (E)-2-methyl-2-butenyl carbonate -Drug Synthesis Database

【结构式】

【分子编号】22426

【品名】methyl (E)-2-methyl-2-butenyl carbonate

【CA登记号】

【分子式】C₇H₁₂O₃

【分子量】144.17048

【元素组成】C 58.32% H 8.39% O 33.29%

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：(XXV)

3) Synthesis of ent-Calanolide A, (-)-calanolide A: The Clemensen reduction of 5,7-dihydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-one (XXI) with Zn/HCl in methanol gives 5,7-dihydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran (XXII), which is condensed with methyl 2-hexynoate (XXIII) using the palladium catalyst Pd2dba3 to yield dihydrobenzodipyran (XXIV). The regio- and enantioselective allylic alkylation of (XXIV) with 2-methyl-2(E)-butenyl carbonate (XXV) catalyzed by Pd2dba3 using a chiral ligand affords the chiral dihydrobenzodipyran ether (XXVI), which is dehydrogenated with dichlorodicyanobenzoquinone (DDQ) in dioxane to (XXVII). The chemoselective hydroboration of (XXVII) with 9-BBN and H2O2 gives the alcohol (XXVIII) with high diastereomeric selectivity. The Dess-Martin oxidation of (XXVIII) yields the expected aldehyde (XXIX), which is cyclized to (10S,11R,12R)-benzotripyran (XXX) (ent-calanolide B). Finally, this compound is converted into ent-calanolide A by inversion of the C-12 hydroxy group carried out with a modified Mitsunobu reaction with dimethyl azodicarboxylate (DEAD)/trimethylphosphine/chloroacetic acid in toluene/THF, followed by treatment with NH4OH in methanol. The authors indicate that Calanolide A can be synthesized in the same way by simply using the mirror image of the chiral ligand in the addition of carbonate (XXV) to dihydrobenzodipyran (XXIV).

参考文献中间体

合成目标

【1】 Castañer, J.; Leeson, P.; Sorbera, L.A.; Calanolide A. Drugs Fut 1999, 24, 3, 235.
【2】 Toste, F.D.; Trost, B.M.; A catalytic enantioselective approach to chromans. J Am Chem Soc 1998, 120, 35, 9074.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXI)	22422	5,7-dihydroxy-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one		C₁₁H₁₂O₄	详情	详情
(XXII)	22423	2,2-dimethyl-5,7-chromanediol		C₁₁H₁₄O₃	详情	详情
(XXIII)	19609	methyl 2-hexynoate	18937-79-6	C₇H₁₀O₂	详情	详情
(XXIV)	22425	5-hydroxy-2,2-dimethyl-10-propyl-3,4-dihydro-2H,8H-pyrano[2,3-f]chromen-8-one		C₁₇H₂₀O₄	详情	详情
(XXV)	22426	methyl (E)-2-methyl-2-butenyl carbonate		C₇H₁₂O₃	详情	详情
(XXVI)	22427	5-[[(1S)-1,2-dimethyl-2-propenyl]oxy]-2,2-dimethyl-10-propyl-3,4-dihydro-2H,8H-pyrano[2,3-f]chromen-8-one		C₂₂H₂₈O₄	详情	详情
(XXVII)	22428	5-[[(1S)-1,2-dimethyl-2-propenyl]oxy]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one		C₂₂H₂₆O₄	详情	详情
(XXVIII)	22429	5-[[(1S,2R)-3-hydroxy-1,2-dimethylpropyl]oxy]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one		C₂₂H₂₈O₅	详情	详情
(XXIX)	22430	(2S,3S)-3-[(2,2-dimethyl-8-oxo-10-propyl-2H,8H-pyrano[2,3-f]chromen-5-yl)oxy]-2-methylbutanal		C₂₂H₂₆O₅	详情	详情
(XXX)	22431	(10S,11R,12S)-12-hydroxy-6,6,10,11-tetramethyl-4-propyl-11,12-dihydro-2H,6H,10H-dipyrano[2,3-f:2,3-h]chromen-2-one		C₂₂H₂₆O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The reaction of 5,7-dihydroxy-4-propyl-2H-1-benzopyran-2-one (I) with TsCl (or MsCl) and pyridine gives the ditosylate (II), which is selectively desulfonated by means of TBAF in THF at 0 C to yield monotosylate (III). The cyclization of (III) with 3-chloro-3-methyl-1-butyne (IV) by means of K2CO3, Bu4N+I- and ZnCl2 in butanone/DMF affords the benzodipyran (V), which is detosylated with TBAF in THF at 20 C to provide the hydroxy derivative (VI). Finally, the OH group of (VI) is enantioselectively alkylated with the mixed carbonate ester (VII) by means of Pd2dba3 ,Cs2CO3 and a (S,S)-chiral ligand in THF to furnish the target chiral intermediate (VIII) (see scheme no. 20433103a, intermediate (XXVII)).

参考文献中间体

合成目标

【1】 Fox, M.E.; et al.; A novel synthesis of 5-hydroxy-2,2-dimethyl-10-propyl-2H-pyrano[2,3-f]chromen-8-one. Tetrahedron Lett 2002, 43, 16, 2899.

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)	22405	5,7-dihydroxy-4-propyl-2H-chromen-2-one		C₁₂H₁₂O₄	详情	详情
(II)	58650	5-{[(4-methylphenyl)sulfonyl]oxy}-2-oxo-4-propyl-2H-chromen-7-yl 4-methylbenzenesulfonate		C₂₆H₂₄O₈S₂	详情	详情
(III)	58651	5-hydroxy-2-oxo-4-propyl-2H-chromen-7-yl 4-methylbenzenesulfonate		C₁₉H₁₈O₆S	详情	详情
(IV)	58652	2,2-dimethyl-8-oxo-10-propyl-2H,8H-pyrano[2,3-f]chromen-5-yl 4-methylbenzenesulfonate		C₂₄H₂₄O₆S	详情	详情
(V)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(VI)	58653	5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one		C₁₇H₁₈O₄	详情	详情
(VII)	22426	methyl (E)-2-methyl-2-butenyl carbonate		C₇H₁₂O₃	详情	详情
(VIII)	22428	5-[[(1S)-1,2-dimethyl-2-propenyl]oxy]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one		C₂₂H₂₆O₄	详情	详情

Extended Information