三丁基膦 → (5S)-3-(3-fluoro-4-imidazol-1-yl-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-one

HRID 8147

反应方程式

HRID 8147 反应方程式
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH2:16][C@H:15]([CH2:17]O)[O:14][C:13]3=[O:19])=[CH:8][C:7]=2[F:20])[CH:5]=[CH:4][N:3]=[CH:2]1.ClC(Cl)(Cl)COC([NH:27][C:28]1[CH:32]=[CH:31][O:30][N:29]=1)=O.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[O:30]1[CH:31]=[CH:32][C:28]([NH:27][CH2:17][C@@H:15]2[O:14][C:13](=[O:19])[N:12]([C:9]3[CH:10]=[CH:11][C:6]([N:1]4[CH:5]=[CH:4][N:3]=[CH:2]4)=[C:7]([F:20])[CH:8]=3)[CH2:16]2)=[N:29]1

参与物

6

反应物 4

HCID 13831三丁基膦HCID 73042偶氮二甲酰二哌啶HCID 12114192,2,2-Trichloroethyl isoxazol-3-ylcarbamateHCID 104927643-(3-Fluoro-4-(imidazol-1-yl)phenyl)-5(R)-hydroxymethyloxazolidin-2-one

产物 1

HCID 497417(5S)-3-(3-fluoro-4-imidazol-1-yl-phenyl)-5-[(isoxazol-3-ylamino)methyl]oxazolidin-2-one收率 158.5%

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂2 次

实验过程

3-(4-Imidazol-1-yl-3-fluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one (693 mg, 2.5 mM, see WO 96-23788) and 3-(2,2,2-trichloroethyloxycarbonylamino)isoxazole (649 mg, 2.5 mM) were suspended by stirring in dry tetrahydrofuran (25 ml) under nitrogen in an ice-bath. Tributylphosphine (808 mg, 4 mM) was added followed by 1,1′-(azodicarbonyl)dipiperidine (945 mg, 3.75 nM) dissolved in tetrahydrofuran (10 ml) over 10 minutes. The mixture was then stirred 18 hours, allowing the temperature to rise to ambient, then filtered, and the filter cake washed with tetrahydrofuran. The combined filtrates were evaporated and the residue purified by chromatography on a 20 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethane. Relevant fractions were combined, evaporated, and the residue triturated with diethyl ether to give the desired product (1.36 g), contaminated with tributylphosphine oxide.

后处理

  1. filtrationthen filtered
  2. washthe filter cake washed with tetrahydrofuran
  3. customThe combined filtrates were evaporated
  4. customthe residue purified by chromatography on a 20 g silica Mega Bond Elut® column
  5. washeluting with
  6. temperaturea gradient increasing in polarity from 0 to 5% methanol in dichloromethane
  7. customevaporated
  8. customthe residue triturated with diethyl ether

来源与证据

ORD记录
ord-a99a9a93cf9f400f97f0c5d45b51636c
来源数据集
uspto-grants-2006_08
专利号
US07087629B2

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