Benzylamine → HCID 20445811, compound

HRID 2418429Notes

Reaction equation

HRID 2418429 reaction equation
[CH2:1]([NH-:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:9]=[C:10]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:11](O)=[O:12].C(N)C1C=CC=CC=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>CN(C)C=O.C(N(CC)CC)C>[CH2:1]([NH:8][C:11](=[O:12])[C:10](=[O:9])[CH2:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 697322-Oxo-4-phenylbutyric acidHCID 199401P,P-Diphenylphosphinic azideHCID 22619318Benzyl amide

Product 1

HCID 20445811HCID 20445811, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

Prepare the benzylamide of 2-oxo-4-phenylbutyric acid by dissolving 3.0 g of this acid, 2.4 ml of benzylamine, and 4.7 ml of diphenylphosphorylazide in 60 ml of cold dimethylformamide and adding dropwise 2.6 ml of triethylamine in DMF, holding the temperature at about -10° C. for 2.5 hours. Store overnight at room temperature, strip off the DMF in vacuo, and partition the residue between water and ethyl acetate. Chromatograph the contents of the organic layer on silica gel, eluting with ethyl acetate:hexane 1:4. Evaporate the solvent from the product fractions to obtain 2.2 g of crystalline N-benzyl-2-oxo-4-phenylbutyramide. Couple 1.26 g of this with 0.19 g of L-Ala-L-Pro using 0.125 g of sodium cyanoborohydride in ethanol in the manner described in Example 44. Purify the crude product by gel filtration (LH-20) to obtain the mixture of diastereoisomers of N-(1-benzylaminocarbonyl-3-phenylpropyl)-L-alanyl-L-proline. The nmr spectrum (CDCl3) shows a doublet at 1.1 ppm (3H) a close pair of singlets at 7.3 (10H), and complex absorption at 1.6-2.3 (6H), 2.3-2.9 (2H), 2.9-3.8 (4H) and 4.0-4.6 (3H). The mass spectrum of silylated material shows prominent peaks at m/e=509 (monosilyl derivative) and 581 (disilyl derivative).

Workup

  1. customat about -10° C.
  2. customfor 2.5 hours
  3. customStore overnight at room temperature, strip off the DMF in vacuo, and partition the residue between water and ethyl acetate
  4. washChromatograph the contents of the organic layer on silica gel, eluting with ethyl acetate:hexane 1:4
  5. customEvaporate the solvent from the product fractions

Sources & evidence

ORD record
ord-45bc108d5e714c7fa898c45c0beaf4e3
Source dataset
uspto-grants-1984_09
Patent number
US04472380

Reaction notes

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