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【结 构 式】

【分子编号】49691

【品名】isobutyl 4-bromo-3-fluorophenylcarbamate

【CA登记号】

【 分 子 式 】C11H13BrFNO2

【 分 子 量 】290.1321632

【元素组成】C 45.54% H 4.52% Br 27.54% F 6.55% N 4.83% O 11.03%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IV)

The reaction of 3-fluoroaniline (I) with isobutyl chloroformate (II) by means of K2CO3 in dichloromethane/water gives the carbamate (III), which is brominated with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) to yield the 4-bromo-3-fluorophenyl carbamate (IV). The condensation of (IV) with tetrahydrothiopyran-4-one (V) by means of EtMgBr and BuLi in THF affords the tertiary alcohol (VI), which is dehydrated by means of TFA in dichloromethane and oxidized with NaIO4 in methanol/water to provide the unsaturated sulfoxide (VII). The stereoselective reduction of (VII) by means of H2 over Pt/C in DMF gives the cis sulfoxide (VIII). The cyclization of the carbamate (VIII) with (S)-3-chloropropane-1,2-diol (IX) by means of Li t-amylate in DMF gives the oxazolidinone (X), whose free OH group is activated with 2,5-dichlorobenzenesulfonyl chloride (XI) and TEA in dichloromethane to yield the sulfonate (XII). The reaction of (XII) with NH4OH in methanol/acetonitrile affords the aminomethyl derivative (XIII), which is finally acylated with acetic anhydride (XIV) to provide the target sulfoxide.

1 Gage, J.R.; et al.; Stereodivergent synthesis of sulfoxide-containing oxazolidinone antibiotics. Tetrahedron Lett 2000, 41, 22, 4301.
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) 13423 1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate 543-27-1 C5H9ClO2 详情 详情
(III) 49690 isobutyl 3-fluorophenylcarbamate C11H14FNO2 详情 详情
(IV) 49691 isobutyl 4-bromo-3-fluorophenylcarbamate C11H13BrFNO2 详情 详情
(V) 49692 Tetrahydrothiopyran-4-one; Tetrahydro-4H-thiopyran-4-one; 4-Oxothiane 1072-72-6 C5H8OS 详情 详情
(VI) 49693 isobutyl 3-fluoro-4-(4-hydroxytetrahydro-2H-thiopyran-4-yl)phenylcarbamate C16H22FNO3S 详情 详情
(VII) 49694 4-[2-fluoro-4-[(isobutoxycarbonyl)amino]phenyl]-3,6-dihydro-2H-thiopyranium-1-olate C16H20FNO3S 详情 详情
(VIII) 49695 4-[2-fluoro-4-[(isobutoxycarbonyl)amino]phenyl]tetrahydro-2H-thiopyranium-1-olate C16H22FNO3S 详情 详情
(IX) 49696 (S)-(+)-Alpha-Chlorohydrin; (S)-(+)-3-Chloro-1,2-propanediol; (S)-3-Chloro-1,2-propanediol 60827-45-4 C3H7ClO2 详情 详情
(X) 49697 4-[2-fluoro-4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]tetrahydro-2H-thiopyranium-1-olate C15H18FNO4S 详情 详情
(XI) 49698 2,5-Dichlorobenzenesulfonic acid 88-42-6 C6H4Cl2O3S 详情 详情
(XII) 49699 4-[4-[(5R)-5-([[(2,5-dichlorophenyl)sulfonyl]oxy]methyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]tetrahydro-2H-thiopyranium-1-olate C21H20Cl2FNO6S2 详情 详情
(XIII) 49700 4-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]tetrahydro-2H-thiopyranium-1-olate C15H19FN2O3S 详情 详情
(XIV) 49701 Acetic anhydride; Acetyl oxide 108-24-7 C4H6O3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

The reaction of 3-fluoroaniline (I) with isobutyl chloroformate (II) by means of K2CO3 in dichloromethane/water gives the carbamate (III), which is brominated with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) to yield the 4-bromo-3-fluorophenyl carbamate (IV). The condensation of (IV) with tetrahydrothiopyran-4-one (V) by means of EtMgBr and BuLi in THF affords the tertiary alcohol (VI), which is dehydroxylated by means of poly(methylhydrosiloxane) (PMHS), (Me3Si)2O and Ts-OH in toluene to provide the intermediate (VII). The stereoselective oxidation of (VII) to the trans sulfoxide (VIII) is performed by means of Ti(OiPr)4 and tert-butyl hydroperoxide in the presence of diisopropyl D-tartrate. The cyclization of the carbamate (VIII) with (S)-3-chloropropane-1,2-diol (IX) by means of Li t-amylate in DMF gives the oxazolidinone (X), whose free OH group is activated with 3-nitrobenzenesulfonyl chloride and TEA in dichloromethane to yield the sulfonate (XII). The reaction of (XII) with NH4OH in methanol/acetonitrile affords the aminomethyl derivative (XIII), which is finally acylated with propionic anhydride (XIV) to provide the target sulfoxide.

1 Gage, J.R.; et al.; Stereodivergent synthesis of sulfoxide-containing oxazolidinone antibiotics. Tetrahedron Lett 2000, 41, 22, 4301.
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) 13423 1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate 543-27-1 C5H9ClO2 详情 详情
(III) 49690 isobutyl 3-fluorophenylcarbamate C11H14FNO2 详情 详情
(IV) 49691 isobutyl 4-bromo-3-fluorophenylcarbamate C11H13BrFNO2 详情 详情
(V) 49692 Tetrahydrothiopyran-4-one; Tetrahydro-4H-thiopyran-4-one; 4-Oxothiane 1072-72-6 C5H8OS 详情 详情
(VI) 49693 isobutyl 3-fluoro-4-(4-hydroxytetrahydro-2H-thiopyran-4-yl)phenylcarbamate C16H22FNO3S 详情 详情
(VII) 49702 isobutyl 3-fluoro-4-tetrahydro-2H-thiopyran-4-ylphenylcarbamate C16H22FNO2S 详情 详情
(VIII) 49706 4-[2-fluoro-4-[(isobutoxycarbonyl)amino]phenyl]tetrahydro-2H-thiopyranium-1-olate C16H22FNO3S 详情 详情
(IX) 49696 (S)-(+)-Alpha-Chlorohydrin; (S)-(+)-3-Chloro-1,2-propanediol; (S)-3-Chloro-1,2-propanediol 60827-45-4 C3H7ClO2 详情 详情
(X) 49707 4-[2-fluoro-4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]tetrahydro-2H-thiopyranium-1-olate C15H18FNO4S 详情 详情
(XI) 49703 m-nitrobenzenesulfonic acid; 3-nitrobenzenesulfonic acid 98-47-5 C6H5NO5S 详情 详情
(XII) 49704 4-[2-fluoro-4-[(5R)-5-([[(3-nitrophenyl)sulfonyl]oxy]methyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]tetrahydro-2H-thiopyranium-1-olate C21H21FN2O8S2 详情 详情
(XIII) 49705 4-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]tetrahydro-2H-thiopyranium-1-olate C15H19FN2O3S 详情 详情
(XIV) 49701 Acetic anhydride; Acetyl oxide 108-24-7 C4H6O3 详情 详情
Extended Information