Ammonium Bicarbonate → N-((1R)-1-carbamoyl-2-phenylethyl)-N-methylcarbamic acid tert.-butylester

HRID 1602011Notes

Reaction equation

HRID 1602011 reaction equation
[C:1]([O:5][C:6]([N:8]([C@H:10]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:11](O)=[O:12])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])O.[NH4+].O.O[N:28]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([C@@H:10]([C:11](=[O:12])[NH2:28])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 14013Ammonium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7015127N-Boc-N-methyl-D-phenylalanine

Product 1

HCID 54512009N-((1R)-1-carbamoyl-2-phenylethyl)-N-methylcarbamic acid tert.-butylesterYield 70.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (2R)-2-(N-tert-butoxycarbonyl-N-methylamino)-3-phenylpropionic acid (4.00 g, 14.32 mmol) in N,N-dimethylformamide (10 ml) was cooled to 0° C. Ammonium hydrogen carbonate (5.66 g, 71.60 mmol) was added as a solid. 1-Hydroxybenzotriazole hydrate (1.94 g, 14.32 mmol) and successively N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (2.75 g, 14.32 mmol) were added. The suspension was stirred for 16 h, while warming up to room temperature. The reaction mixture was diluted with ethyl acetate (150 ml) and extracted with saturated sodium chloride solution/water (200 ml/300 ml). The aqueous phase was extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash-chromatography on silica (70 g), using ethyl acetate/heptane as eluent, to give 2.80 g of N-((1R)-1-carbamoyl-2-phenylethyl)-N-methylcarbamic acid tert.-butylester.

Workup

  1. extractionextracted with saturated sodium chloride solution/water (200 ml/300 ml)
  2. extractionThe aqueous phase was extracted with ethyl acetate (3×100 ml)
  3. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customThe crude product was purified by flash-chromatography on silica (70 g)

Sources & evidence

ORD record
ord-bb8b6fe6357344559258d963b0ac4ad1
Source dataset
uspto-grants-1999_11
Patent number
US05977178

Reaction notes

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