(2R)-Oxiran-2-ylmethyl butanoate → (5R)-3-(3-fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one

HRID 1108571ノート

反応式

HRID 1108571 の反応式
C(O[C:9]([NH:11][C:12]1[CH:13]=[CH:14][C:15]([N:19]2[CH2:24][CH2:23][N:22]([CH3:25])[C:21](=[O:26])[CH2:20]2)=[C:16]([F:18])[CH:17]=1)=O)C1C=CC=CC=1.C([Li])CCC.[CH2:32]([O:36][C:37](=[O:41])CCC)[C@@H:33]1[O:35]C1>C1COCC1>[F:18][C:16]1[CH:17]=[C:12]([N:11]2[CH2:9][C@H:32]([CH2:33][OH:35])[O:36][C:37]2=[O:41])[CH:13]=[CH:14][C:15]=1[N:19]1[CH2:24][CH2:23][N:22]([CH3:25])[C:21](=[O:26])[CH2:20]1

参加物

5

反応物 3

HCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 187839085-Benzyloxycarbonylamino-2-(4-methyl-3-oxopiperazin-1-yl)fluorobenzeneHCID 178418339Butyllithium

生成物 1

HCID 54288185(5R)-3-(3-fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

5-Benzyloxycarbonylamino-2-(4-methyl-3-oxopiperazin-1-yl)fluorobenzene (4.5 g) was dissolved in dry THF (100 ml) under argon and the solution cooled to -78° C. A solution of n-butyllithium (8.67 ml, 1.6 M in hexane) was added to this whilst keeping the temperature below -60° C. The mixture was stirred for 5 minutes and (R)-glycidylbutyrate (1.86 ml) was added. Stirring was continued at -78° C. for 30 minutes and the temperature then allowed to rise to ambient over 16 hours. The mixture was evaporated to dryness and then treated with dichloromethane. The mixture was filtered to give (5R)-3-(3-fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one (409 mg). The residual organic solution was washed twice with water, and then brine. After drying (MgSO4) and evaporation of solvent, the residue was chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 6% methanol in dichloromethane. Relevant fractions were combined and evaporated to give further (5R)-3-(3-fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one product (535 mg).

後処理

  1. customthe temperature below -60° C
  2. stirringStirring
  3. waitwas continued at -78° C. for 30 minutes
  4. waitto ambient over 16 hours
  5. customThe mixture was evaporated to dryness
  6. additiontreated with dichloromethane
  7. filtrationThe mixture was filtered

出典と根拠

ORDレコード
ord-057a30188b17418cb0cb60d582b60c12
出典データセット
uspto-grants-2000_05
特許番号
US06069145

反応ノート

読み込み中…