3-(3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one -Drug Synthesis Database

【结构式】

【分子编号】60315

【品名】3-(3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one

【CA登记号】

【分子式】C₁₀H₁₀FNO₃

【分子量】211.1927432

【元素组成】C 56.87% H 4.77% F 9% N 6.63% O 22.73%

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：(IV)

Reaction of 3-fluoroaniline (I) with benzyl chloroformate provides carbamate (II). The lithium derivative of (II) is then condensed with (R)-glycidyl butyrate (III) to yield the chiral oxazolidinone (IV). After conversion of alcohol (IV) to the corresponding mesylate (V), displacement with NaN3 in hot DMF gives rise to the alkyl azide (VI). Catalytic hydrogenation of azide (VI) furnishes amine (VII), which is further acylated with acetic anhydride, producing acetamide (VIII). Aromatic iodination of (VIII) by means of iodine monochloride in the presence of trifluoroacetic acid gives (IX). Iodide compound (IX) is then converted into the aryl stannane (X) upon treatment with hexamethyl ditin and palladium catalyst

参考文献中间体

合成目标

【1】 Im, W.; Lee, T.; Cho, J.; Choi, S.; Rhee, J.; In vitro and in vivo studies of hetero-ring substituted pyridine containing oxazolidinone derivatives, including DA-7867. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1311.
【2】 Lee, J.-G.; Lee, J.-J.; Park, S.-K.; Lee, T.-H.; Leem, W.-B.; Cho, J.-H.; Choi, S.-H.; Kim, D.-G.; Sung, H.-J. (Dong-A Pharmaceutical Co., Ltd.); Novel oxazolidinone derivs. and a process for the preparation thereof. WO 0194342 .

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)	20697	3-fluoroaniline; 3-fluorophenylamine	372-19-0	C₆H₆FN	详情	详情
(II)	60314	phenylmethyl 3-fluorophenylcarbamate		C₁₄H₁₂FNO₂	详情	详情
(III)	18385	(2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate	60456-26-0	C₇H₁₂O₃	详情	详情
(IV)	60315	3-(3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one		C₁₀H₁₀FNO₃	详情	详情
(V)	60316	[3-(3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl methanesulfonate		C₁₁H₁₂FNO₅S	详情	详情
(VI)	60317	(R)-5-(azidomethyl)-3-(3-fluorophenyl)oxazolidin-2-one		C₁₀H₉FN₄O₂	详情	详情
(VII)	60318	5-(aminomethyl)-3-(3-fluorophenyl)-1,3-oxazolidin-2-one		C₁₀H₁₁FN₂O₂	详情	详情
(VIII)	60319	N-{[3-(3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide		C₁₂H₁₃FN₂O₃	详情	详情
(IX)	38138	N-[[(5S)-3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide		C₁₂H₁₂FIN₂O₃	详情	详情
(X)	60320	N-({3-[3-fluoro-4-(trimethylstannanyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide		C₁₅H₂₁FN₂O₃Sn	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

3-Fluoroaniline (I) is condensed with benzyl chloroformate to give carbamate (II). Reaction of (II) with (R)-glycidol butyrate (III) in the presence of butyllithium affords oxazolidinone (IV). After conversion of alcohol (IV) to the corresponding mesylate, displacement with NaN3 provides azide (V). Reduction and acylation of (V) by means of thioacetic acid leads to acetamide (VI). Friedel-Crafts acylation of the aromatic ring of (VI) with acetic anhydride in the presence of methanesulfonic acid furnishes acetophenone (VII). Acidic hydrolysis of acetamide (VII) yields amine (VIII). This is then treated with thiophosgene, followed by methanol, to produce the thiocarbamate (IX). Finally, aldol condensation of the acetophenone (IX) with pyridine-2-carbaldehyde (X) gives rise to the target compound.

参考文献中间体

合成目标

【1】 Selvakumar, N.; et al.; Synthesis and antibacterial activity of novel chalcone oxazolidinone hybrids. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1323.

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)	20697	3-fluoroaniline; 3-fluorophenylamine	372-19-0	C₆H₆FN	详情	详情
(II)	60314	phenylmethyl 3-fluorophenylcarbamate		C₁₄H₁₂FNO₂	详情	详情
(III)	18385	(2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate	60456-26-0	C₇H₁₂O₃	详情	详情
(IV)	60315	3-(3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one		C₁₀H₁₀FNO₃	详情	详情
(V)	60317	(R)-5-(azidomethyl)-3-(3-fluorophenyl)oxazolidin-2-one		C₁₀H₉FN₄O₂	详情	详情
(VI)	60319	N-{[3-(3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide		C₁₂H₁₃FN₂O₃	详情	详情
(VII)	62789	N-{[(5S)-3-(4-acetyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide		C₁₄H₁₅FN₂O₄	详情	详情
(VIII)	62790	(5S)-3-(4-acetyl-3-fluorophenyl)-5-(aminomethyl)-1,3-oxazolidin-2-one		C₁₂H₁₃FN₂O₃	详情	详情
(IX)	62791	O-methyl [(5S)-3-(4-acetyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methylcarbamothioate		C₁₄H₁₅FN₂O₄S	详情	详情
(X)	25173	2-pyridinecarbaldehyde	1121-60-4	C₆H₅NO	详情	详情

Extended Information