(2S)oxiranylmethyl butyrate -Drug Synthesis Database

【结构式】

【分子编号】17017

【品名】(2S)oxiranylmethyl butyrate

【CA登记号】

【分子式】C₇H₁₂O₃

【分子量】144.17048

【元素组成】C 58.32% H 8.39% O 33.29%

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：(VI)

The condensation of morpholine (I) with 3,4-difluoronitrobenzene (II) by means of diisopropylethylamine in refluxing acetonitrile gives 3-fluoro-4-(4-morpholinyl)nitrobenzene (III), which is reduced with ammonium formate over Pd/C in THF/methanol to the corresponding aniline (IV). The reaction of (IV) with benzyloxycarbonyl chloride and NaHCO3 in acetone/water yields the carbamate ester (V), which is cyclized with 2(R),3-epoxypropyl butyrate (VI) by means of butyllithium in THF affording 5(R)-(hydroxymethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]oxazolidin-2-one (VII). The reaction of (VII) with methanesulfonyl chloride and triethylamine in dichloromethane gives the mesylate (VIII), which by reaction with NaN3 in hot DMF is converted into the azide (IX). The reduction of (IX) with H2 over Pd/C in ethyl acetate affords the corresponding amine (X), which is finally acetylated with acetic anhydride and pyridine.

参考文献中间体

合成目标

【1】 Brickner, S.J.; Hutchinson, D.K.; Barbachyn, M.R.; et al.; Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant Gram-positive bacterial infections. J Med Chem 1996, 39, 3, 673.
【2】 Lizondo, J.; Rabasseda, X.; Castañer, J.; Linezolid. Drugs Fut 1996, 21, 11, 1116.
【3】 Barbachyn, M.R.; Brickner, S.J.; Hutchinson, D.K. (Pharmacia Corp.); Substd. oxazine and thiazine oxazolidinone antimicrobials. EP 0717738; JP 1997502436; WO 9507271 .

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)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(II)	17013	1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene	369-34-6	C₆H₃F₂NO₂	详情	详情
(III)	17014	4-(2-fluoro-4-nitrophenyl)morpholine		C₁₀H₁₁FN₂O₃	详情	详情
(IV)	17015	3-fluoro-4-morpholinophenylamine; 3-fluoro-4-morpholinoaniline; 3-fluoro-4-(4-morpholinyl)phenylamine; 3-Fluoro-4-(4-morpholinyl)benzeneamine	93246-53-8	C₁₀H₁₃FN₂O	详情	详情
(V)	17016	benzyl N-(3-fluoro-4-morpholinophenyl)carbamate		C₁₈H₁₉FN₂O₃	详情	详情
(VI)	17017	(2S)oxiranylmethyl butyrate		C₇H₁₂O₃	详情	详情
(VII)	17018	(5R)-3-(3-fluoro-4-morpholinophenyl)-5-(hydroxymethyl)-1,3-oxazolan-2-one	168828-82-8	C₁₄H₁₇FN₂O₄	详情	详情
(VIII)	17019	[(5R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-1,3-oxazolan-5-yl]methyl methanesulfonate	174649-09-3	C₁₅H₁₉FN₂O₆S	详情	详情
(IX)	17020	(5R)-5-(azidomethyl)-3-(3-fluoro-4-morpholinophenyl)-1,3-oxazolan-2-one		C₁₄H₁₆FN₅O₃	详情	详情
(X)	17021	(5S)-5-(aminomethyl)-3-(3-fluoro-4-morpholinophenyl)-1,3-oxazolan-2-one		C₁₄H₁₈FN₃O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The condensation of the protected 3,5-difluoroaniline (I) with 1-benzyl-4-piperidone (II) by means of BuLi in THF gives 4-(1-benzyl-4-hydroxypiperidin-4-yl)-3,5-difluoroaniline (III), which is dehydrated with refluxing conc. HCl to yield the tetrahydropyridine (IV). The reaction of (IV) with benzyl chloroformate in acetone/water affords the carbamate (V), which is cyclized with (R)-glycidyl butyrate (VI) by means of BuLi in THF to provide the oxazolidinone (VII). The condensation of (VII) with isoxazol-3-ol (VIII) by means of PPh3 and DIAD in THF gives the expected ether adduct (IX), which is debenzylated by reaction with 1-chloroethyl chloroformate in dichloromethane, yielding the free tetrahydropyridine derivative (X). The condensation of (X) with (S)-2,3-O-isopropylideneglyceric acid (XI) by means of DEC or DCC and TEA in dichloromethane affords the corresponding acyl tetrahydropyridine (XII), which is finally deprotected with HCl in THF to provide the target dihydroxy compound.

参考文献中间体

合成目标

【1】 Gravestock, M.B. (AstraZeneca plc); Oxazolidinone derivs., process for their preparation and pharmaceutical compsns. containing them. EP 1082323; JP 2002517498; WO 9964417 .
【2】 Gravestock, M.B.; Warren, K.E.H.; Ennis, D.S.; Currie, A.C.; Ainge, D. (AstraZeneca AB; AstraZeneca plc); Chemical processes and intermedies. WO 0140236 .

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)	59481	1-(3,5-difluorophenyl)-2,2,5,5-tetramethyl-1,2,5-azadisilolidine		C₁₂H₁₉F₂NSi₂	详情	详情
(II)	15720	1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one	3612-20-2	C₁₂H₁₅NO	详情	详情
(III)	59482	4-(4-amino-2,6-difluorophenyl)-1-benzyl-4-piperidinol		C₁₈H₂₀F₂N₂O	详情	详情
(IV)	59483	4-(1-benzyl-1,2,3,6-tetrahydro-4-pyridinyl)-3,5-difluorophenylamine; 4-(1-benzyl-1,2,3,6-tetrahydro-4-pyridinyl)-3,5-difluoroaniline		C₁₈H₁₈F₂N₂	详情	详情
(V)	59484	benzyl 4-(1-benzyl-1,2,3,6-tetrahydro-4-pyridinyl)-3,5-difluorophenylcarbamate		C₂₆H₂₄F₂N₂O₂	详情	详情
(VI)	17017	(2S)oxiranylmethyl butyrate		C₇H₁₂O₃	详情	详情
(VII)	59485	(5R)-3-[4-(1-benzyl-1,2,3,6-tetrahydro-4-pyridinyl)-3,5-difluorophenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one		C₂₂H₂₂F₂N₂O₃	详情	详情
(VIII)	59486	3-isoxazolol		C₃H₃NO₂	详情	详情
(IX)	59487	(5R)-3-[4-(1-benzyl-1,2,3,6-tetrahydro-4-pyridinyl)-3,5-difluorophenyl]-5-[(3-isoxazolyloxy)methyl]-1,3-oxazolidin-2-one		C₂₅H₂₃F₂N₃O₄	详情	详情
(X)	59488	(5R)-3-[3,5-difluoro-4-(1,2,3,6-tetrahydro-4-pyridinyl)phenyl]-5-[(3-isoxazolyloxy)methyl]-1,3-oxazolidin-2-one		C₁₈H₁₇F₂N₃O₄	详情	详情
(XI)	59489	(4S)-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid		C₆H₁₀O₄	详情	详情
(XII)	59490	(5R)-3-[4-(1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]carbonyl}-1,2,3,6-tetrahydro-4-pyridinyl)-3,5-difluorophenyl]-5-[(3-isoxazolyloxy)methyl]-1,3-oxazolidin-2-one		C₂₄H₂₅F₂N₃O₇	详情	详情

Extended Information