dipropyl (1S)-2-chloro-2-(hydroxyimino)-1-methylethylphosphonate -Drug Synthesis Database

【结构式】

【分子编号】60651

【品名】dipropyl (1S)-2-chloro-2-(hydroxyimino)-1-methylethylphosphonate

【CA登记号】

【分子式】C₉H₁₉ClNO₄P

【分子量】271.680662

【元素组成】C 39.79% H 7.05% Cl 13.05% N 5.16% O 23.56% P 11.4%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(I)

The reaction of the oxime (I) with the 1-methylallyl alcohol (II) by means of Et-MgBr gives the isoxazoline (III), which is condensed with 2-methylthiazole-4-carbaldehyde (IV) by means of DBU and LiCl in acetonitrile to yield the adduct (V). The oxidation of (V) with TPAP and NMO affords the methyl ketone (VI), which is condensed with the Grignard reagent (VII) in THF to provide the tertiary alcohol (VIII). The protection of (VIII) by means of Tes-OTf gives the silylated compound (IX), which is oxidated with SmI2 in THF to yield the beta-hydroxy ketone (X). The reduction of (X) with Et3B and NaBH4 in THF/methanol affords the beta-diol (XI), which is treated with SOCl2, TEA and TBAF to provide the epoxide derivative (XII). The silylation of both OH groups of (XII) by means of Tes-Cl and TEA in dichloromethane furnishes the bis-silyl ether (XIII), which is selectively monodesilylated by means of AcOH in THF/water to give the primary alcohol (XIV). The oxidation of this alcohol by means of TPAP and NMO yields the carbaldehyde (XV).

参考文献中间体

合成目标

【1】 Bode, J.W.; Carreira, E.M.; Stereoselective syntheses of epothilones A and B via nitrile oxide cycloadditions and related studies. J Org Chem 2001, 66, 19, 6410.

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)	60651	dipropyl (1S)-2-chloro-2-(hydroxyimino)-1-methylethylphosphonate		C₉H₁₉ClNO₄P	详情	详情
(II)	49287	(2R)-3-buten-2-ol	33447-72-2	C₄H₈O	详情	详情
(III)	60652	diethyl (1S)-1-{(5R)-5-[(1R)-1-hydroxyethyl]-4,5-dihydro-3-isoxazolyl}ethylphosphonate		C₁₁H₂₂NO₅P	详情	详情
(IV)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(V)	49289	(1R)-1-[(5R)-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,5-dihydro-5-isoxazolyl]-1-ethanol		C₁₂H₁₆N₂O₂S	详情	详情
(VI)	49290	1-[(5R)-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,5-dihydro-5-isoxazolyl]-1-ethanone		C₁₂H₁₄N₂O₂S	详情	详情
(VII)	49291	bromo[(4S)-4-methyl-5-[(triisopropylsilyl)oxy]pentyl]magnesium		C₁₅H₃₃BrMgOSi	详情	详情
(VIII)	49292	(2R,6S)-6-methyl-2-[(5R)-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,5-dihydro-5-isoxazolyl]-7-[(triisopropylsilyl)oxy]-2-heptanol		C₂₇H₄₈N₂O₃SSi	详情	详情
(IX)	49293	(5R)-5-[(1R,5S)-1,5-dimethyl-1-[(triethylsilyl)oxy]-6-[(triisopropylsilyl)oxy]hexyl]-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,5-dihydroisoxazole; (1R,5S)-1,5-dimethyl-1-[(5R)-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,5-dihydro-5-isoxazolyl]-6-[(triisopropylsilyl)oxy]hexyl triethylsilyl ether		C₃₃H₆₂N₂O₃SSi₂	详情	详情
(X)	60653	(E,5R,6R,10S)-5-hydroxy-2,6,10-trimethyl-1-(2-methyl-1,3-thiazol-4-yl)-6-[(triethylsilyl)oxy]-11-[(triisopropylsilyl)oxy]-1-undecen-3-one		C₃₃H₆₃NO₄SSi₂	详情	详情
(XI)	49294	(E,3S,5R,6R,10S)-2,6,10-trimethyl-1-(2-methyl-1,3-thiazol-4-yl)-6-[(triethylsilyl)oxy]-11-[(triisopropylsilyl)oxy]-1-undecene-3,5-diol		C₃₃H₆₅NO₄SSi₂	详情	详情
(XII)	60654	(2S,3E)-1-{(2S,3R)-3-[(4S)-5-hydroxy-4-methylpentyl]-3-methyloxiranyl}-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-buten-2-ol		C₁₈H₂₉NO₃S	详情	详情
(XIII)	60655	(2S)-2-methyl-5-((2R,3S)-2-methyl-3-{(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl}oxiranyl)pentyl triethylsilyl ether; 2-methyl-4-{(E,3S)-2-methyl-4-((2S,3R)-3-methyl-3-{(4S)-4-methyl-5-[(triethylsilyl)oxy]pentyl}oxiranyl)-3-[(triethylsilyl)oxy]-1-butenyl}-1,3-thiazole		C₃₀H₅₇NO₃SSi₂	详情	详情
(XIV)	49297	(2S)-2-methyl-5-((2R,3S)-2-methyl-3-[(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl]oxiranyl)-1-pentanol		C₂₄H₄₃NO₃SSi	详情	详情
(XV)	49278	(2S)-2-methyl-5-((2R,3S)-2-methyl-3-[(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl]oxiranyl)pentanal		C₂₄H₄₁NO₃SSi	详情	详情

Extended Information