N-Methylbenzylamine → tert-butyl (S)-2-[benzyl(methyl)amino]-2-oxo-1-phenylethylcarbamate

HRID 498881Notes

Reaction equation

HRID 498881 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.[CH3:45][NH:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>ClCCl>[CH2:47]([N:46]([CH3:45])[C:10](=[O:12])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

6

Reactant 4

HCID 7669N-MethylbenzylamineHCID 10868DicyclohexylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11010409(2S)-2-(((tert-butoxy)carbonyl)amino)-2-phenylacetic acid

Product 1

HCID 59711000tert-butyl (S)-2-[benzyl(methyl)amino]-2-oxo-1-phenylethylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
2.5 °C

Procedure

(S)-N-tert-butoxycarbonyl-2-phenylglycine (250 g) and 1-hydroxybenzotriazole hydrate (136.2 g) and N,N′-dicyclohexylcarbodimide (205.1 g) were combined in dichloromethane (3000 mL) at 0-5° C. and the mixture stirred for 15 minutes. A solution of N-methylbenzylamine (128.1 mL) in dichloromethane (835 mL) was added slowly, maintaining 0-5° C. The resulting slurry was allowed to warm to room temperature overnight before being filtered, washing the by-product solids with dichloromethane (500 mL). The combined filtrate was twice washed with saturated aqueous sodium hydrogen carbonate (2×1500 mL), twice washed with 50% saturated aqueous sodium hydrogen carbonate solution (2×1500 mL), once washed with 2.5% aqueous citric acid solution (1500 mL) and once washed with demineralized water (1500 mL), providing a dichloromethane solution of tert-butyl (S)-2-[benzyl(methyl)amino]-2-oxo-1-phenylethylcarbamate. Analysis by chiral HPLC showed that 2% of the wrong enantiomer (tert-butyl (R)-2-[benzyl(methyl)amino]-2-oxo-1-phenylethylcarbamate) to be present at this stage.

Workup

  1. temperatureto warm to room temperature overnight
  2. filtrationbefore being filtered
  3. washwashing the by-product solids with dichloromethane (500 mL)
  4. washThe combined filtrate was twice washed with saturated aqueous sodium hydrogen carbonate (2×1500 mL)
  5. washtwice washed with 50% saturated aqueous sodium hydrogen carbonate solution (2×1500 mL)
  6. washonce washed with 2.5% aqueous citric acid solution (1500 mL)
  7. washonce washed with demineralized water (1500 mL)

Sources & evidence

ORD record
ord-b684f57b5d7346fda7b6160b6cd1d069
Source dataset
uspto-grants-2005_09
Patent number
US06949572B2

Reaction notes

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