Benzaldehyde → HCID 21609903, compound

HRID 79747Notes

Reaction equation

HRID 79747 reaction equation
[NH2:1][CH2:2][CH:3]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:4]([OH:6])=[O:5].[CH:15](=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH2:23](N(CC)CC)C.[BH4-].[Na+].C[Si](C=[N+]=[N-])(C)C>CO.C1(C)C=CC=CC=1>[CH3:23][O:5][C:4](=[O:6])[CH:3]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:2][NH:1][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 5

HCID 240BenzaldehydeHCID 8471TriethylamineHCID 167693TrimethylsilyldiazomethaneHCID 32971953-Amino-2-{[(tert-butoxy)carbonyl]amino}propanoic acidHCID 4311764Sodium borohydride

Product 1

HCID 21609903HCID 21609903, compoundYield 54.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 1140TolueneSolvent

Procedure

3-Amino-2-tert-butoxycarbonylamino-propionic acid (5.0 g, 24.5 mmol) was suspended in methanol (100 mL) and benzaldehyde (5.2 g, 49 mmol) was added, followed by triethylamine (TEA, 10.2 mL, 73.5 mmol). The reaction mixture was stirred at ambient temperature for 90 minutes and cooled to 0° C. Solid sodium borohydride (2.78 g, 73.5 mmol) was added in small portions and the reaction was stirred for additional 60 minutes after addition was complete. All volatiles were removed in vacuo and the crude was dissolved in NaOHaq (0.1 M, 100 mL). The solution was washed with diethyl ether and acidified with HCl aq. The mixture was extracted with chloroform. The organic extracts were washed with brine and dried over sodium sulfate. Filtration and evaporation of solvents in vacuo yielded crude semi-solid (9.0 g). The crude material was dissolved in methanol (40 mL) and toluene (20 mL) and the solution was cooled to 0° C. Trimethysilyl diazomethane solution (2M, in hexanes) was added until the yellow color persisted (˜25 mL). The reaction mixture was stirred for additional 60 minutes at room temperature. The volatiles were removed in vacuo and the crude product was purified via silica gel chromatography (eluent: EtOAc/hexanes) to yield the pure product 3-Benzylamino-2-tert-butoxycarbonylamino-propionic acid methyl ester (4.09 g): LCMS-ESI+: calc'd for C16H24N2O4: 308.3 (M+). Found: 309.2 (M+H+).

Workup

  1. temperaturecooled to 0° C
  2. stirringthe reaction was stirred for additional 60 minutes
  3. additionafter addition
  4. customAll volatiles were removed in vacuo
  5. dissolutionthe crude was dissolved in NaOHaq (0.1 M, 100 mL)
  6. washThe solution was washed with diethyl ether
  7. extractionwas extracted with chloroform
  8. washThe organic extracts were washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationFiltration and evaporation of solvents in vacuo
  11. customyielded crude semi-solid (9.0 g)
  12. stirringThe reaction mixture was stirred for additional 60 minutes at room temperature
  13. customThe volatiles were removed in vacuo
  14. customthe crude product was purified via silica gel chromatography (eluent: EtOAc/hexanes)

Sources & evidence

ORD record
ord-a6daea6f7cf74b33ac47ca7c8cb9fbe8
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Reaction notes

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