allyl tert-butyl carbonate -Drug Synthesis Database

【结构式】

【分子编号】62295

【品名】allyl tert-butyl carbonate

【CA登记号】

【分子式】C₈H₁₄O₃

【分子量】158.19736

【元素组成】C 60.74% H 8.92% O 30.34%

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：(II)

Alkylation of clarithromycin diacetate (I) with allyl t-butyl carbonate (II) in the presence of palladium catalyst affords the 11-O-allyl ether (III). Subsequent metathesis reaction between ally ether (III) and 1-butenyl-4-phenylimidazole (IV) employing Grubb's catalyst provides adduct (V). Finally, methanolysis of the 2'-acetate ester of (V) gives rise to the target compound.

参考文献中间体

合成目标

【1】 Niu, D.; Phan, L.T.; Haley, T.; Polemeropoulos, A.; Or, Y.; Syntheses and antibacterial activities of novel 11-O-substituted macrolide and ketolide derivatives. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1666.
【2】 Or, Y.S.; Phan, L.T.; Niu, D. (Enanta Pharmaceuticals, Inc.); 11-O-Substd. macrolides and their descladinose derivs.. US 2003114396; US 6673774; WO 0347600 .

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)	53089	(2S,3S,4R,6R)-6-[((3R,4S,5R,6R,7R,9R,11R,12R,13S,14R)-6-{[(2S,3R,4S,6R)-3-(acetyloxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecanyl)oxy]-4-methoxy-2,4-dimethyltetrahydro-2H-pyran-3-yl acetate	n/a	C₄₂H₇₃NO₁₅	详情	详情
(II)	62295	allyl tert-butyl carbonate		C₈H₁₄O₃	详情	详情
(III)	62680	(2S,3S,4R,6R)-6-{[(3R,4S,5R,6R,7R,9R,11R,12R,13S,14R)-6-{[(2S,3R,4S,6R)-3-(acetyloxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy}-12-(allyloxy)-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecanyl]oxy}-4-		C₄₅H₇₇NO₁₅	详情	详情
(IV)	62681	1-(3-butenyl)-4-phenyl-1H-imidazole		C₁₃H₁₄N₂	详情	详情
(V)	62682	(2S,3S,4R,6R)-6-[((3R,4S,5R,6R,7R,9R,11R,12R,13S,14R)-6-{[(2S,3R,4S,6R)-3-(acetyloxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-12-{[(E)-5-(4-phenyl-1H-imidazol-1-yl)-2-		C₅₆H₈₇N₃O₁₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

The obtained 15 methylerythromycin A (XI) is chemically modified as follows. Treatment of ketone (XI) with hydroxylamine and AcOH provides oxime (XII), which is further converted into oxime acetal (XIV) by condensation with 1,1-diisopropoxycyclohexane (XIII) in the presence of PPTS. The sugar hydroxyl groups of (XIV) are then protected by silylation with trimethylsilyl chloride/trimethylsilyl imidazole to yield the 2',4''-bis-silyl ether (XV). Then, alkylation of the 6-hydroxyl group of (XV) with allyl t-butyl carbonate (XVI) in the presence of Pd(OAc)2 provides allyl ether (XVII). Further acidic hydrolysis of the acetal and silyl ether groups of (XVII) affords oxime (XVIII).

参考文献中间体

合成目标

【1】 Macielag, M.; Abbanat, D.; Ashley, G.; Foleno, B.; Fu, H.; Li, Y.; Wira, E.; Bush, K.; Structure-activity studies of 15-methyl ketolides: Optimization of the heterocyclic substituent. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1662.
【2】 Hlasta, D.; Khosla, C.; Chu, D.T.W.; Ashley, G.; Henninger, T.C.; Grant, E.B. (Ortho-McNeil Pharmaceutical, Inc.); Ketolide antibacterials. WO 0232918 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	62291	(3R,4S,5R,6R,7S,9R,11R,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-3,5,7,9,11,13-hexamethyl-14-pr		C₃₈H₆₉NO₁₃	详情	详情
(XII)	62292	(3R,4S,5R,6R,7S,9R,11S,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-3,5,7,9,11,13-hexamethyl-14-pr		C₃₈H₇₀N₂O₁₃	详情	详情
(XIII)	45909	1-isopropoxycyclohexyl isopropyl ether; 1,1-diisopropoxycyclohexane	1132-95-2	C₁₂H₂₄O₂	详情	详情
(XIV)	62293	(3R,4S,5R,6R,7S,9R,11S,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-3,5,7,9,11,13-hexamethyl-14-pr		C₄₇H₈₆N₂O₁₄	详情	详情
(XV)	62294	(3R,4S,5R,6R,7S,9R,11S,12R,13S,14R)-6-({(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-3-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}oxy)-7,12,13-trihydroxy-4-({(2R,4R,5S,6S)-4-methoxy-4,6-dimethyl-5-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}oxy)-3,		C₅₃H₁₀₂N₂O₁₄Si₂	详情	详情
(XVI)	62295	allyl tert-butyl carbonate		C₈H₁₄O₃	详情	详情
(XVII)	62296	(3R,4S,5R,6R,7S,9R,11S,12R,13S,14R)-7-(allyloxy)-6-({(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-3-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}oxy)-12,13-dihydroxy-4-({(2R,4R,5S,6S)-4-methoxy-4,6-dimethyl-5-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-		C₅₆H₁₀₆N₂O₁₄Si₂	详情	详情
(XVIII)	62297	(3R,4S,5R,6R,7S,9R,11S,12R,13S,14R)-7-(allyloxy)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-12,13-dihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-3,5,7,9,11,13-hexame		C₄₁H₇₄N₂O₁₃	详情	详情

Extended Information