4-Chlorobenzaldehyde → (R)-2-(4-chloro-benzylamino)-3-methyl-butyric acid methyl ester

HRID 271611

反応式

HRID 271611 の反応式
Cl.[CH3:2][O:3][C:4](=[O:10])[C@H:5]([NH2:9])[CH:6]([CH3:8])[CH3:7].[Cl:11][C:12]1[CH:19]=[CH:18][C:15]([CH:16]=O)=[CH:14][CH:13]=1.C(N(CC)CC)C.[BH4-].[Na+]>C(Cl)Cl.[O-]S([O-])(=O)=O.[Mg+2].CO>[CH3:2][O:3][C:4](=[O:10])[C@H:5]([NH:9][CH2:16][C:15]1[CH:18]=[CH:19][C:12]([Cl:11])=[CH:13][CH:14]=1)[CH:6]([CH3:8])[CH3:7]

参加物

8

反応物 4

HCID 77264-ChlorobenzaldehydeHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 11984198Methyl D-valinate hydrochloride

生成物 1

HCID 8150601(R)-2-(4-chloro-benzylamino)-3-methyl-butyric acid methyl ester収率 97%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 24083Sulfuric acid magnesium salt (1:1)溶媒

実験手順

3 g (18 mmoles) of (R)-2-amino-3-methyl-butyric acid methyl ester hydrochloride, 2.1 g (15 mmoles) of 4-chloro-benzaldehyde and 2.94 ml (21 mmoles) of triethyl amine are dissolved in 100 ml of CH2Cl2 and excess of MgSO4 is added at ambient temperature under N2 atmosphere. After being stirred for 18 hours at ambient temperature, the reaction mixture is filtered off and washed with CH2Cl2. The filtrate is concentrated under reduced pressure. To the crude imine in 250 ml of MeOH, 2.04 g (54 mmoles) of NaBH4 is added portionwise at 0° C. The reaction mixture is stirred at 0° C. for 2 hours and concentrated to ¼ of whole volume under reduced pressure. The mixture is extracted with AcOEt and the combined extracts are washed with sat. NaHCO3 and brine, dried over Na2SO4 and concentrated under reduced pressure to give 3.72 g of desired (R)-2-(4-chloro-benzylamino)-3-methyl-butyric acid methyl ester in 97% yield.

後処理

  1. additionis added at ambient temperature under N2 atmosphere
  2. filtrationthe reaction mixture is filtered off
  3. washwashed with CH2Cl2
  4. concentrationThe filtrate is concentrated under reduced pressure
  5. stirringThe reaction mixture is stirred at 0° C. for 2 hours
  6. concentrationconcentrated
  7. extractionThe mixture is extracted with AcOEt
  8. washthe combined extracts are washed with sat. NaHCO3 and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-aca9aa7d68bd4897b31cc18c0fd04ce7
出典データセット
uspto-grants-2008_11
特許番号
US07452886B2

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