Dichloromethane → N-((R)-methylphenylphosphinyl)-N-benzyl-D-leucine methyl ester

HRID 355444Notes

Reaction equation

HRID 355444 reaction equation
[CH3:1][P:2](Cl)([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3].[CH3:11][O:12][C:13](=[O:24])[C@@H:14]([CH3:23])[NH:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CN1[CH2:31][CH2:30]OCC1.Cl[CH2:33]Cl>CN(C)C1C=CN=CC=1>[CH3:11][O:12][C:13](=[O:24])[C@@H:14]([CH2:23][CH:30]([CH3:31])[CH3:33])[N:15]([P@@:2]([CH3:1])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 79724-MethylmorpholineHCID 21983Methyl(phenyl)phosphinoyl chlorideHCID 10987118methyl (2R)-2-(benzylamino)propanoate

Product 1

HCID 54435063N-((R)-methylphenylphosphinyl)-N-benzyl-D-leucine methyl ester

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Conditions

Temperature
0 °C

Procedure

Methylphenyl-phosphinic chloride (361 mg, 2.07 mmol) is dissolved in dichloromethane (2.5 mL) and then cooled to 0° C. To this is added a solution of N-benzyl D-alanine methyl ester (400 mg, 2.07 mmol) and N-methyl morpholine (0.51 mL, 4.6 mmol) in dichloromethane (2.5 mL). A catalytic amount of 4-dimethylaminopyridine is then added to the stirring mixture. The reaction is stirred for 16 hours at room temperature, washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified by silica gel flash chromatography (100% ethyl acetate) to give N-((R)-methylphenylphosphinyl)-N-benzyl-D-leucine methyl ester as an oil.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product is purified by silica gel flash chromatography (100% ethyl acetate)

Sources & evidence

ORD record
ord-b613748248924102a45235909ca86e36
Source dataset
uspto-grants-1998_11
Patent number
US05830915

Reaction notes

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