di(tert-butyl) phosphonate -Drug Synthesis Database

【结构式】

【分子编号】42237

【品名】di(tert-butyl) phosphonate

【CA登记号】13086-84-5

【分子式】C₈H₁₉O₃P

【分子量】194.210822

【元素组成】C 49.48% H 9.86% O 24.71% P 15.95%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(III)

Treatment of cinnarizine (I) with phosphate (IV) in acetonitrile in the presence of the proton scavenger 1,2,2,6,6-pentamethylpiperidine affords cinarizinium chloride (II), which is finally treated with TFA in benzene to yield the target trifluoroacetate derivative. Phosphate (IV) can be obtained from phosphite (III) by first treatment with KHCO3 and KMnO4 followed by conversion to tetramethylammonium di-tert-butylphosphate by means of tetramethylammonium hydroxide and final treatment with chloroiodomethane (A) in refluxing dimethoxyethane.

参考文献中间体

合成目标

【1】 Krise, J.P.; et al.; Novel prodrug approach for tertiary amines: Synthesis and preliminary evaluation of N-phosphonooxymethyl prodrugs. J Med Chem 1999, 42, 16, 3094.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	42238	chloro(iodo)methane	593-71-5	CH₂ClI	详情	详情
(I)	42242	1-benzhydryl-4-[(E)-3-phenyl-2-propenyl]piperazine	298-57-7	C₂₆H₂₈N₂	详情	详情
(II)	42243	4-benzhydryl-1-([[di(tert-butoxy)phosphoryl]oxy]methyl)-1-[(E)-3-phenyl-2-propenyl]piperazin-1-ium chloride		C₃₅H₄₈ClN₂O₄P	详情	详情
(III)	42237	di(tert-butyl) phosphonate	13086-84-5	C₈H₁₉O₃P	详情	详情
(IV)	42239	di(tert-butyl) chloromethyl phosphate;di-tert-butyl chloromethyl phosphate；PHOSPHORIC ACI DI-T-BUTYL EXTER CHLOROMETHYL ESTER	229625-50-7	C₉H₂₀ClO₄P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Loxapine (I) is treated with phosphate (IV) in acetonitrile in the presence of the proton scavenger 1,2,2,6,6-pentamethylpiperidine to afford loxapinium chloride (II), which is finally treated with TFA in benzene to yield the target trifluoroacetate derivative. Phosphate (IV) can be obtained from phosphite (III) by treatment with KHCO3 and KMnO4 followed by conversion to tetramethylammonium di-tert-butylphosphate by means of tetramethylammonium hydroxide and final treatment with chloroiodomethane (A) in refluxing dimethoxyethane.

参考文献中间体

合成目标

【1】 Krise, J.P.; et al.; Novel prodrug approach for tertiary amines: Synthesis and preliminary evaluation of N-phosphonooxymethyl prodrugs. J Med Chem 1999, 42, 16, 3094.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	42238	chloro(iodo)methane	593-71-5	CH₂ClI	详情	详情
(I)	42240	11-(4-methyl-1-piperazinyl)dibenzo[b,f][1,4]oxazepine		C₁₈H₁₉N₃O	详情	详情
(II)	42241	4-dibenzo[b,f][1,4]oxazepin-11-yl-1-([[di(tert-butoxy)phosphoryl]oxy]methyl)-1-methylpiperazin-1-ium chloride		C₂₇H₃₉ClN₃O₅P	详情	详情
(III)	42237	di(tert-butyl) phosphonate	13086-84-5	C₈H₁₉O₃P	详情	详情
(IV)	42239	di(tert-butyl) chloromethyl phosphate;di-tert-butyl chloromethyl phosphate；PHOSPHORIC ACI DI-T-BUTYL EXTER CHLOROMETHYL ESTER	229625-50-7	C₉H₂₀ClO₄P	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Addition of di-tert-butyl phosphite (II) to the pyridine aldehyde (I) afforded the pyridylphosphonate (III). The tert-butyl phosphonate esters and the cyclic ketal groups of (III) were then hydrolyzed under acidic conditions to furnish the title compound.

参考文献中间体

合成目标

【1】 Haque, W. (Medicure Inc.); Cardioprotective phosphonates and malonates. WO 0164692 .

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)	28771	2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine-5-carbaldehyde		C₁₁H₁₃NO₃	详情	详情
(II)	42237	di(tert-butyl) phosphonate	13086-84-5	C₈H₁₉O₃P	详情	详情
(III)	53403	di(tert-butyl) hydroxy(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methylphosphonate	n/a	C₁₉H₃₂NO₆P	详情	详情

Extended Information