Acetone → (2R)-(4-chlorophenyl)(cyclopropyl)ethanoic acid

HRID 1835028

反応式

HRID 1835028 の反応式
CC(C)=O.[OH-].[Na+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH:19]2[CH2:21][CH2:20]2)[C:15]([O:17]C)=[O:16])=[CH:10][CH:9]=1>O>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([C@@H:14]([CH:19]2[CH2:21][CH2:20]2)[C:15]([OH:17])=[O:16])=[CH:12][CH:13]=1

参加物

5

反応物 3

HCID 180AcetoneHCID 14798Sodium Hydroxide2 回HCID 21274166Methyl 2-cyclopropyl-2-(4-chlorophenyl)acetate

生成物 1

HCID 28292965(2R)-(4-chlorophenyl)(cyclopropyl)ethanoic acid収率 37.9%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

Horse liver esterase (4.6 g horse liver acetone powder, Sigma Chemical Co.) is suspended in water (200 ml) at room temperature and the pH is adjusted to 7.5 with 1.0 M sodium hydroxide. Methyl (2RS)-(4-chlorophenyl)(cyclopropyl)ethanoate (7.0 g, 31.4 mol) is added and stirring is continued at room temperature with the addition of 1.0 M sodium hydroxide as needed to maintain the pH at 7.1-8.0. After 14 ml of base had been consumed, the pH was brought to 3 with 10% hydrochloric acid, ethyl acetate is added and the mixture is filtered through diatomaceous earth. The organic phase is washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Flash chromatography affords (2R)-(4-chlorophenyl)(cyclopropyl)ethanoic acid (2.5 g, 37.9%) and recovered ester (4.1 g). The ester was resubjected to the hydrolysis conditions with additional horse liver esterase (1.0 g ) for an extended period during which an additional 4.4 ml of 1.0 M sodium hydroxide is consumed. Acidification, workup and purification as described above affords methyl (2S)-(4-chlorophenyl)(cyclopropyl)ethanoate (3.1 g, 36.2%) The enantiomeric excess of (2R)-(4-chlorophenyl)(cyclopropyl)ethanoic acid (as the methyl ester) and (2R)-(4-chlorophenyl)(cyclopropyl)ethanoic acid are determined with the chiral NMR shift reagent Eu(hfc)3 to be >96:4 and >98:2 respectively.

後処理

  1. temperatureto maintain the pH at 7.1-8.0
  2. customAfter 14 ml of base had been consumed
  3. additionis added
  4. filtrationthe mixture is filtered through diatomaceous earth
  5. washThe organic phase is washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-d0ffa0efc51b4b20a19284024a6cdca3
出典データセット
uspto-grants-2004_08
特許番号
US06770463B2

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