(2S)-N-methoxy-2-[(4-methoxybenzyl)oxy]-N-methyl-4-(phenylsulfonyl)butanamide -Drug Synthesis Database

【结构式】

【分子编号】63111

【品名】(2S)-N-methoxy-2-[(4-methoxybenzyl)oxy]-N-methyl-4-(phenylsulfonyl)butanamide

【CA登记号】

【分子式】C₂₀H₂₅NO₆S

【分子量】407.48764

【元素组成】C 58.95% H 6.18% N 3.44% O 23.56% S 7.87%

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：(IX)

The intermediate carbaldehyde (VI) and Weinreb amide (IX) have been obtained as follows. The reaction of tetrahydropyranyl glycidol (I) with methyl phenylsulfone (II) by means of BuLi in THF gives the secondary alcohol (III), which is protected with Pmb-Cl and NaH in DMF to yield the diether (IV). Selective cleavage of the THP group of (IV) by means of CSA in methanol affords the primary alcohol (V), which is oxidized with (COCl)2 and DMSO in dichloromethane to provide the aldehyde (VI). Further oxidation of (VI) by means of NaClO2 in t-butanol gives the carboxylic acid (VII), which is finally condensed with N,O-dimethylhydroxylamine (VIII) by means of iso-butyl chloroformate in dichloromethane to yield the intermediate Weinreb amide (IX).

参考文献中间体

合成目标

【1】 Ghosh, A.K.; Wang, Y.; Kim, J.T.; Total synthesis of microtubule-stabilizing agent (-)-laulimalide. J Org Chem 2001, 66, 26, 8973.

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)	63105	2-[(2R)oxiranyloxy]tetrahydro-2H-pyran; (2R)oxiranyl tetrahydro-2H-pyran-2-yl ether		C₇H₁₂O₃	详情	详情
(II)	23622	methyl phenyl sulfone; methyl(dioxo)phenyl-lambda(6)-sulfane	3112-85-4	C₇H₈O₂S	详情	详情
(III)	63106	(2S)-4-(phenylsulfonyl)-1-(tetrahydro-2H-pyran-2-yloxy)-2-butanol		C₁₅H₂₂O₅S	详情	详情
(IV)	63107	2-{[(2S)-2-[(4-methoxybenzyl)oxy]-4-(phenylsulfonyl)butyl]oxy}tetrahydro-2H-pyran; (3S)-3-[(4-methoxybenzyl)oxy]-4-(tetrahydro-2H-pyran-2-yloxy)butyl phenyl sulfone		C₂₃H₃₀O₆S	详情	详情
(V)	63108	(2S)-2-[(4-methoxybenzyl)oxy]-4-(phenylsulfonyl)-1-butanol		C₁₈H₂₂O₅S	详情	详情
(VI)	63109	(2S)-2-[(4-methoxybenzyl)oxy]-4-(phenylsulfonyl)butanal		C₁₈H₂₀O₅S	详情	详情
(VII)	63110	(2S)-2-[(4-methoxybenzyl)oxy]-4-(phenylsulfonyl)butanoic acid		C₁₈H₂₀O₆S	详情	详情
(VIII)	13361	(Methoxyamino)methane; N,O-Dimethylhydroxylamine	1117-97-1	C₂H₇NO	详情	详情
(IX)	63111	(2S)-N-methoxy-2-[(4-methoxybenzyl)oxy]-N-methyl-4-(phenylsulfonyl)butanamide		C₂₀H₂₅NO₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

The intermediate phenyl sulfone (XXIII) has been obtained as follows. The reaction of tetrahydropyranyl glycidol (I) with isopropenyl bromide (X) by means of CuCN in THF gives the secondary alcohol (XI), which is treated with allyl bromide (XII) and KH in THF to yield the allyl ether (XIII). A ring closing metathesis reaction with (XIII) catalyzed by a Ru catalyst yields the protected dihydropyran derivative (XIV), which is treated with CSA in methanol to afford the carbinol (XV). The oxidation of (XV) with (COCl)2 and DMSO in dichloromethane provides the carbaldehyde (XVI), which is treated with CBr4 and PPh3 in dichloromethane to give the dibromovinyl derivative (XVII). The condensation of (XVII) with the intermediate aldehyde (VI) by means of BuLi in THF yields the propargyl alcohol derivative (XVIII), which is oxidized with DMP to the corresponding acetylenic ketone (XIX). Alternatively, acetylenic ketone (XIX) can also be obtained by condensation of dibromovinyl derivative (XVII) with the intermediate Weinreb amide (IX) by means of BuLi in THF. The enantioselective reduction of ketone (XIX) with L-Selectride in THF affords the chiral propargyl alcohol (XX), which is reduced with Red-Al and treated with TFA to provide the trans-allylic alcohol (XXI). The reaction of the diol (XXI) with Pmp-CH(OEt)2 and CSA gives the acetal (XXII), which is finally reduced with DIBAL in dichloromethane to yield the intermediate Pmb-protected phenyl sulfone (XXIII).

参考文献中间体

合成目标

【1】 Ghosh, A.K.; Wang, Y.; Kim, J.T.; Total synthesis of microtubule-stabilizing agent (-)-laulimalide. J Org Chem 2001, 66, 26, 8973.

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)	63105	2-[(2R)oxiranyloxy]tetrahydro-2H-pyran; (2R)oxiranyl tetrahydro-2H-pyran-2-yl ether		C₇H₁₂O₃	详情	详情
(VI)	63109	(2S)-2-[(4-methoxybenzyl)oxy]-4-(phenylsulfonyl)butanal		C₁₈H₂₀O₅S	详情	详情
(IX)	63111	(2S)-N-methoxy-2-[(4-methoxybenzyl)oxy]-N-methyl-4-(phenylsulfonyl)butanamide		C₂₀H₂₅NO₆S	详情	详情
(X)	42375	2-bromo-1-propene；2-bromopropene;Isopropenyl bromide;a-Methylvinyl bromide	557-93-7	C₃H₅Br	详情	详情
(XI)	63112	(2S)-4-methyl-1-(tetrahydro-2H-pyran-2-yloxy)-4-penten-2-ol		C₁₁H₂₀O₃	详情	详情
(XII)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(XIII)	63113	allyl (1S)-3-methyl-1-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-butenyl ether; 2-{[(2S)-2-(allyloxy)-4-methyl-4-pentenyl]oxy}tetrahydro-2H-pyran		C₁₄H₂₄O₃	详情	详情
(XIV)	63114	2-{[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methoxy}tetrahydro-2H-pyran; [(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methyl tetrahydro-2H-pyran-2-yl ether		C₁₂H₂₀O₃	详情	详情
(XV)	61173	[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methanol		C₇H₁₂O₂	详情	详情
(XVI)	61148	(2S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde		C₇H₁₀O₂	详情	详情
(XVII)	63115	(2S)-2-(2,2-dibromovinyl)-4-methyl-3,6-dihydro-2H-pyran		C₈H₁₀Br₂O	详情	详情
(XVIII)	63116	(4S)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexyn-3-ol		C₂₆H₃₀O₆S	详情	详情
(XIX)	63117	(4S)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexyn-3-one		C₂₆H₂₈O₆S	详情	详情
(XX)	63118	(3S,4S)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexyn-3-ol		C₂₆H₃₀O₆S	详情	详情
(XXI)	63119	(E,3S,4S)-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexene-3,4-diol		C₁₈H₂₄O₅S	详情	详情
(XXII)	63120	2-((4S,5S)-2-(4-methoxyphenyl)-5-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-1,3-dioxolan-4-yl)ethyl phenyl sulfone; (2S)-2-((E)-2-{(4S,5S)-2-(4-methoxyphenyl)-5-[2-(phenylsulfonyl)ethyl]-1,3-dioxolan-4-yl}ethenyl)-4-methyl-3,6-dihydro-2H-pyran		C₂₆H₃₀O₆S	详情	详情
(XXIII)	63121	(3S,4S,5E)-4-[(4-methoxybenzyl)oxy]-6-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1-(phenylsulfonyl)-5-hexen-3-ol		C₂₆H₃₂O₆S	详情	详情

Extended Information