tert-butyl (1S)-2-oxo-1-phenylethylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】45428

【品名】tert-butyl (1S)-2-oxo-1-phenylethylcarbamate

【CA登记号】

【分子式】C₁₃H₁₇NO₃

【分子量】235.28292

【元素组成】C 66.36% H 7.28% N 5.95% O 20.4%

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：(IV)

A new method for the synthesis of the docetaxel side-chain has been reported: The esterification of (S)-phenylglycine (I) with SOCl2 and methanol gives the corresponding methyl ester (II), which is acylated with tert-butoxycarbonyl anhydride to the tert-butoxycarbonyl derivative (III). The reduction of (III) with dibutylaluminum hydride (DIBAL) in toluene yields the corresponding aldehyde (IV), which is condensed with 2-(trimethylsilyl)thiazole (V) by means of tetrabutylammonium fluoride (TBAF) to afford the (1R,2S)-N-[2-hydroxy-1-phenyl-2-(2-thiazolyl)ethyl]carbamic acid tert-butyl ester (VI) with 88% enantiomeric purity. The cyclization of (VI) with 2,2-dimethoxypropane (VII) catalyzed by camphosulfonic acid (CSA) gives (4S,5R)-3-(tert-butoxycarbonyl)-2,3-dimethyl-4-phenyl-5-(2-thiazolyl)ox azolidine (VIII), which is treated with methyl trifluoromethanesulfonate to afford (4S,5R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyloxazolidine-5-carb aldehyde (IX). Finally, this compound is oxidized with KMnO4 in tert-butanol/aqueous potassium phosphate buffer to yield the corresponding carboxylic acid, the (4S,5R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyloxazolidine-5-carb oxylic acid (X), the side-chain of taxotere suitably protected.

参考文献中间体

合成目标

【1】 Semola, T.; Dondoni, A.; Perrone, D.; Synthesis of Taxol and Taxotere side chains by 2-(trimethylsilyl)thiazole based homologation of L-phenylglycine. Synthesis 1995, 2, 2, 181.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13214	Di-tert-butyldicarbonate; Dicarbonic acid bis(1,1-dimethylethyl) ester; dicarbonic acid di-tert-butyl ester pyrocarbonic acid di-tert-butyl ester; bis(1,1-dimethylethyl) dicarbonate di-tert-butyl pyrocarbonate	24424-99-5	C₁₀H₁₈O₅	详情	详情
(I)	10716	(2S)-2-Amino-2-phenylethanoic acid; L-(+)-alpha-Phenylglycine	2935-35-5	C₈H₉NO₂	详情	详情
(II)	10717	methyl (2S)-2-amino-2-phenylethanoate		C₉H₁₁NO₂	详情	详情
(III)	12485	methyl (2S)-2-[(tert-butoxycarbonyl)amino]-2-phenylethanoate		C₁₄H₁₉NO₄	详情	详情
(IV)	45428	tert-butyl (1S)-2-oxo-1-phenylethylcarbamate		C₁₃H₁₇NO₃	详情	详情
(V)	10720	2-(Trimethylsilyl)-1,3-thiazole	79265-30-8	C₆H₁₁NSSi	详情	详情
(VI)	12488	tert-butyl N-[(1S,2R)-2-hydroxy-1-phenyl-2-(1,3-thiazol-2-yl)ethyl]carbamate		C₁₆H₂₀N₂O₃S	详情	详情
(VII)	10722	1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane	77-76-9	C₅H₁₂O₂	详情	详情
(VIII)	12490	tert-butyl (4S,5R)-2,2-dimethyl-4-phenyl-5-(1,3-thiazol-2-yl)-1,3-oxazolane-3-carboxylate		C₁₉H₂₄N₂O₃S	详情	详情
(IX)	12491	tert-butyl (4S,5R)-5-formyl-2,2-dimethyl-4-phenyl-1,3-oxazolane-3-carboxylate		C₁₇H₂₃NO₄	详情	详情
(X)	12492	(4S,5R)-3-(tert-Butoxycarbonyl)-2,2-dimethyl-4-phenyl-1,3-oxazolane-5-carboxylic acid		C₁₇H₂₃NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

The reaction of 1(R)-phenylethane-1,2-diol (I) with N-hydroxyphthalimide (II) by means of DEAD and PPh3 gives the N-alcoxyphthalimide (III) with(S)-configuration. The hydrazinolysis of (III) with hydrazine hydrate affords the O-alkylhydroxylamine (IV), which is condensed with benzaldehyde (V) to provide the alkylated benzaldoxime (VI). The alkylation of the oxime (VI) with vinyl lithium (VII) in toluene gives the N, O dialkylated hydroxylamine (VIII), which is treated with Zn and AcOH to yield 1(R)-phenylallylamine (IX). The protection of the amine (IX) with Boc2O and NaOH affords the carbamate (X), which is oxidized at the vinyl double bond by means of OsO4 and NaIO4 to provide the acetaldehyde (XI). The reaction of aldehyde (XI) with allylmagnesium bromide (XII) in ethyl ether gives the aminoalcohol (XIII), which is protected with Tbdms-Cl and imidazole to yield the silyl ether (XIV).

参考文献中间体

合成目标

【1】 Yamazaki, N.; et al.; Nucleophilic addition of methyllithium to chiral oxime ethers: Asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue. Tetrahedron Lett 2001, 42, 30, 5029.

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)	56141	(R)-(-)-1-Phenyl-1,2-ethanediol; (R)-(-)-alpha,beta-Dihydroxyethylbenzene; (R)-(-)-Phenyl-1,2-ethanediol; (R)-(-)-Styrene glycol; (-)-Styrene glycol	16355-00-3	C₈H₁₀O₂	详情	详情
(II)	13505	N-Hydroxyphthalimide; 2-Hydroxy-1H-isoindole-1,3(2H)-dione	524-38-9	C₈H₅NO₃	详情	详情
(III)	56142	2-{[(1S)-2-hydroxy-1-phenylethyl]oxy}-1H-isoindole-1,3(2H)-dione		C₁₆H₁₃NO₄	详情	详情
(IV)	56143	(2S)-2-(aminooxy)-2-phenyl-1-ethanol		C₈H₁₁NO₂	详情	详情
(V)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(VI)	62256	benzaldehyde O-[(1S)-2-hydroxy-1-phenylethyl]oxime		C₁₅H₁₅NO₂	详情	详情
(VII)	42368	vinyllithium	917-57-7	C₂H₃Li	详情	详情
(VIII)	62257	(2S)-2-phenyl-2-({[(1R)-1-phenyl-2-propenyl]amino}oxy)-1-ethanol		C₁₇H₁₉NO₂	详情	详情
(IX)	62258	(1R)-1-phenyl-2-propenylamine; (1R)-1-phenyl-2-propen-1-amine		C₉H₁₁N	详情	详情
(X)	62259	tert-butyl (1R)-1-phenyl-2-propenylcarbamate		C₁₄H₁₉NO₂	详情	详情
(XI)	45428	tert-butyl (1S)-2-oxo-1-phenylethylcarbamate		C₁₃H₁₇NO₃	详情	详情
(XII)	61128			C₄H₈	详情	详情
(XIII)	62260	tert-butyl (1S)-2-hydroxy-1-phenyl-4-pentenylcarbamate		C₁₆H₂₃NO₃	详情	详情
(XIV)	62261	tert-butyl (1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-4-pentenylcarbamate		C₂₂H₃₇NO₃Si	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

The esterification of L-phenylglycine (I) with AcCl and methanol gives the methyl ester (II), which is N-protected by means of Boc2O and TEA to yield the N-Boc derivative (III). The reduction of (III) with NaBH4 in ethanol/THF affords the alcohol (IV), which is oxidized by means of (COCl)2 and DMSO to provide the carbaldehyde (V). The reaction of (V) with vinylmagnesium bromide (VI) in THF gives the allyl alcohol (VII), which is protected with Tbdms-Cl and imidazole to yield the silyl ether (VIII). The alkylation of (VIII) with allyl bromide (IX) and NaH in DMF affords the N-allyl derivative (X), which is desilylated by means of TBAF and AcOH in THF to provide the allyl alcohol (XI). The ring closing metathesis reaction of (XI) with a Grubbs' catalyst in dichloromethane gives the tetrahydropyridine (XII), which is treated with H2 over Pd/C in ethanol to yield the chiral protected piperidine (XIII). The condensation of (XIII) with 3,5-bis(trifluoromethyl)benzyl bromide (XIV) by means of NaH in DMF affords the benzyl ether (XV), which is finally deprotected with TFA to provide the target piperidine.

参考文献中间体

合成目标

【1】 Bhaskar, G.; Rao, B.V.; Stereoselective synthesis of L-733,060. Tetrahedron Lett 2003, 44, 5, 915.

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)	10716	(2S)-2-Amino-2-phenylethanoic acid; L-(+)-alpha-Phenylglycine	2935-35-5	C₈H₉NO₂	详情	详情
(II)	10717	methyl (2S)-2-amino-2-phenylethanoate		C₉H₁₁NO₂	详情	详情
(III)	12485	methyl (2S)-2-[(tert-butoxycarbonyl)amino]-2-phenylethanoate		C₁₄H₁₉NO₄	详情	详情
(IV)	59225	(R)-N-(tert-Butoxycarbonyl)-phenylglycinol; N-t-BOC-D-phenylglycinol	102089-74-7	C₁₃H₁₉NO₃	详情	详情
(V)	45428	tert-butyl (1S)-2-oxo-1-phenylethylcarbamate		C₁₃H₁₇NO₃	详情	详情
(VI)	16524	bromo(vinyl)magnesium	1826-67-1	C₂H₃BrMg	详情	详情
(VII)	64501	tert-butyl (1S,2S)-2-hydroxy-1-phenyl-3-butenylcarbamate		C₁₅H₂₁NO₃	详情	详情
(VIII)	64502	tert-butyl (1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-3-butenylcarbamate		C₂₁H₃₅NO₃Si	详情	详情
(IX)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(X)	64503	tert-butyl allyl((1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-3-butenyl)carbamate		C₂₄H₃₉NO₃Si	详情	详情
(XI)	64504	tert-butyl allyl[(1S,2S)-2-hydroxy-1-phenyl-3-butenyl]carbamate		C₁₈H₂₅NO₃	详情	详情
(XII)	64505	tert-butyl (2S,3S)-3-hydroxy-2-phenyl-3,6-dihydro-1(2H)-pyridinecarboxylate		C₁₆H₂₁NO₃	详情	详情
(XIII)	64499	tert-butyl (2S,3S)-3-hydroxy-2-phenyl-1-piperidinecarboxylate		C₁₆H₂₃NO₃	详情	详情
(XIV)	27677	1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene	32247-96-4	C₉H₅BrF₆	详情	详情
(XV)	64500	tert-butyl (2S,3S)-3-{[3,5-bis(trifluoromethyl)benzyl]oxy}-2-phenyl-1-piperidinecarboxylate		C₂₅H₂₇F₆NO₃	详情	详情

Extended Information