tert-butyl 2-hydroxyethylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】32500

【品名】tert-butyl 2-hydroxyethylcarbamate

【CA登记号】26690-80-2

【分子式】C₇H₁₅NO₃

【分子量】161.20104

【元素组成】C 52.16% H 9.38% N 8.69% O 29.78%

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：(XV)

The condensation of 2-(4-hydroxyphenyl)acetic acid methyl ester (XIII) with 2-(tert-butoxycarbonylamino)ethanol (XV) by means of diethyl azodicarboxylate (DEAD) in THF gives 2-[4-[2-(tert-butoxy carbonyl- amino)ethoxy]phenyl]acetic acid methyl ester (XVI), which is deprotected with TFA in dichloromethane yielding the 2-aminoethoxy derivative (XVII). The addition of (XVII) to the oxiranyl derivative (XVIII) in refluxing methanol affords the intermediate (XIX), which is reduced with SnCl2 in refluxing methanol to give the 6-aminopyridine derivative (XX). Finally, this compound is hydrolyzed to the target compound with KOH in methanol/water. The oxirane intermediate (XVIII) has been obtained by stereocontrolled reductive cyclization of 6-(2-bromoacetyl)tetrazolo[1,5-a]pyridine (XXI) with commercial (R)-Alpine Borane in THF.

参考文献中间体

合成目标

【1】 Fisher, M.H.; Wyvratt, M.J. (Merck & Co., Inc.); Novel beta-adrenergic agonists. AU 9047392; EP 0377488; JP 1990231486; US 5030640 .
【2】 Dow, R.L. (Pfizer Inc.); beta-Adrenergic agonists. EP 0824519; JP 1999504649; US 5977124; WO 9635671 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	15822	Methyl 4-hydroxyphenylacetate; methyl 2-(4-hydroxyphenyl)acetate	14199-15-6	C₉H₁₀O₃	详情	详情
(XV)	32500	tert-butyl 2-hydroxyethylcarbamate	26690-80-2	C₇H₁₅NO₃	详情	详情
(XVI)	32501	methyl 2-(4-[2-[(tert-butoxycarbonyl)amino]ethoxy]phenyl)acetate		C₁₆H₂₃NO₅	详情	详情
(XVII)	32502	methyl 2-[4-(2-aminoethoxy)phenyl]acetate		C₁₁H₁₅NO₃	详情	详情
(XVIII)	32504	6-[(2R)oxiranyl][1,2,3,4]tetraazolo[1,5-a]pyridine		C₇H₆N₄O	详情	详情
(XIX)	32503	methyl 2-[4-(2-[[(2R)-2-hydroxy-2-[1,2,3,4]tetraazolo[1,5-a]pyridin-6-ylethyl]amino]ethoxy)phenyl]acetate		C₁₈H₂₁N₅O₄	详情	详情
(XX)	32505	methyl 2-[4-(2-[[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethoxy)phenyl]acetate		C₁₈H₂₃N₃O₄	详情	详情
(XXI)	32506	2-bromo-1-[1,2,3,4]tetraazolo[1,5-a]pyridin-6-yl-1-ethanone		C₇H₅BrN₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

2-Amino-1,3-propanediol (I) was reacted with in situ generated trifluoromethanesulfonyl azide, and the resulting 2-azido compound was purified by chromatography after conversion to the diacetate ester (II). Deacetylation of (II) with sodium methoxide gave 2-azido-1,3-propanediol (III), which was condensed with tosylate (IV) in the presence of NaH to produce the dihydroxyether (V). The primary alcohol group of (V) was then protected as the mono-silyl derivative (VI) employing tert-butyldiphenylsilyl chloride. After acylation of the free hydroxyl group of (VI) with the unsaturated acid (VII), the resulting ester (VIII) was desilylated by using HF in acetonitrile to yield alcohol (IX). The phosphorylating reagent (XII) was prepared by treatment of allyl phosphorodiamidite (X) with N-Boc-ethanolamine (XI). Phosphitylation of alcohol (IX) with phosphoramidite (XII), followed by oxidation of the intermediate phosphite ester with oxone , furnished phosphate (XIII). The azido group of (XIII) was then reduced to the corresponding amine (XIV) by employing (PhS)2Sn.

参考文献中间体

合成目标

【1】 Rossignol, D.P.; Ishizaka, S.T.; Nault, A.; Lewis, M.; Rose, J.; McGuiness, P.; Hawkins, L.D. (Eisai Co., Ltd.); Immunological adjuvant cpd.. EP 1147117; US 6290973; WO 0044758 .

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)	23333	2-amino-1,3-propanediol; serinol	534-03-2	C₃H₉NO₂	详情	详情
(II)	49119	3-(acetoxy)-2-azidopropyl acetate		C₇H₁₁N₃O₄	详情	详情
(III)	49120	2-azido-1,3-propanediol		C₃H₇N₃O₂	详情	详情
(IV)	49121	(3R)-3-hydroxydecyl 4-methylbenzenesulfonate		C₁₇H₂₈O₄S	详情	详情
(V)	49122	(3R)-1-(2-azido-3-hydroxypropoxy)-3-decanol		C₁₃H₂₇N₃O₃	详情	详情
(VI)	49123	(3R)-1-(2-azido-3-[[tert-butyl(diphenyl)silyl]oxy]propoxy)-3-decanol		C₂₉H₄₅N₃O₃Si	详情	详情
(VII)	49124	(Z)-5-dodecenoic acid		C₁₂H₂₂O₂	详情	详情
(VIII)	49125	(1R)-1-[2-(2-azido-3-[[tert-butyl(diphenyl)silyl]oxy]propoxy)ethyl]octyl (Z)-5-dodecenoate		C₄₁H₆₅N₃O₄Si	详情	详情
(IX)	49126	(1R)-1-[2-(2-azido-3-hydroxypropoxy)ethyl]octyl (Z)-5-dodecenoate		C₂₅H₄₇N₃O₄	详情	详情
(X)	49127			C₁₅H₃₃N₂OP	详情	详情
(XI)	32500	tert-butyl 2-hydroxyethylcarbamate	26690-80-2	C₇H₁₅NO₃	详情	详情
(XII)	49128			C₁₆H₃₃N₂O₄P	详情	详情
(XIII)	49129	(1R)-9-(allyloxy)-6-azido-1-heptyl-16,16-dimethyl-9,14-dioxo-4,8,10,15-tetraoxa-13-aza-9lambda(5)-phosphaheptadec-1-yl (Z)-5-dodecenoate		C₃₅H₆₅N₄O₉P	详情	详情
(XIV)	49130	(1R)-9-(allyloxy)-6-amino-1-heptyl-16,16-dimethyl-9,14-dioxo-4,8,10,15-tetraoxa-13-aza-9lambda(5)-phosphaheptadec-1-yl (Z)-5-dodecenoate		C₃₅H₆₇N₂O₉P	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Methyl 2,6-difluorobenzoate (I) was converted to the hydroxamic acid (II) upon treatment with hydroxylamine and KOH. Cyclization of the fluorobenzohydroxamic acid (II) using KOH in boiling butanol produced the 3-hydroxybenzisoxazole (III), which was subjected to Mitsunobu coupling with N-Boc-ethanolamine (IV) to furnish the N-Boc-aminoethyl ether (V). Metalation of (V) with butyllithium at -70 C, followed by quenching with iodomethane gave rise to two regioisomeric methylbenzisoxazoles (VI) and (VII), which were separated by column chromatography. The target 7-methyl benzisoxazole (VII) was then deprotected under acidic conditions to yield the title aminoethoxy derivative.

参考文献中间体

合成目标

【1】 Kojima, K.; Aizawa, Y.; Kaneko, I.; Sakai, J.; Kozuka, M.; Koyama, K.; Samata, N.; Yoshimi, K. (Sankyo Co., Ltd.); Isoxazoles. EP 0779281; JP 1997059264; US 5965591; US 6096771; WO 9606837 .

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)	58771	2,6-Difluorobenzoic acid methyl ester; Methyl 2,6-difluorobenzoate	13671-00-6	C₈H₆F₂O₂	详情	详情
(II)	58772	2,6-difluoro-N-hydroxybenzamide		C₇H₅F₂NO₂	详情	详情
(III)	58773	4-fluoro-1,2-benzisoxazol-3-ol		C₇H₄FNO₂	详情	详情
(IV)	32500	tert-butyl 2-hydroxyethylcarbamate	26690-80-2	C₇H₁₅NO₃	详情	详情
(V)	58774	tert-butyl 2-[(4-fluoro-1,2-benzisoxazol-3-yl)oxy]ethylcarbamate		C₁₄H₁₇FN₂O₄	详情	详情
(VI)	58775	tert-butyl 2-[(4-fluoro-5-methyl-1,2-benzisoxazol-3-yl)oxy]ethylcarbamate		C₁₅H₁₉FN₂O₄	详情	详情
(VII)	58776	tert-butyl 2-[(4-fluoro-7-methyl-1,2-benzisoxazol-3-yl)oxy]ethylcarbamate		C₁₅H₁₉FN₂O₄	详情	详情

Extended Information