Diethyl Ether → N-propionyl-L-alanyl-L-proline anilide

HRID 1448731Notes

Reaction equation

HRID 1448731 reaction equation
C(O[C:9]([NH:11][C@H:12]([C:14]([N:16]1[CH2:29][CH2:28][CH2:27][C@H:17]1[C:18]([NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:19])=[O:15])[CH3:13])=[O:10])C1C=CC=CC=1.[CH3:30][CH2:31]OCC.C(OC(=O)CC)(=O)CC>Br.C(O)(=O)C>[C:9]([NH:11][C@H:12]([C:14]([N:16]1[CH2:29][CH2:28][CH2:27][C@H:17]1[C:18]([NH:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:19])=[O:15])[CH3:13])(=[O:10])[CH2:30][CH3:31]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 31263Propionic anhydrideHCID 35369893HCID 35369893, compound

Product 1

HCID 54376826N-propionyl-L-alanyl-L-proline anilide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 260Hydrogen BromideSolvent

Procedure

8.7 g (0.022 mol) of N-benzyloxycarbonyl-L-alanyl-L-proline anilide were dissolved in 40 ml of 4-N hydrogen bromide in acetic acid and the solution was stirred at room temperature for 1 hour. Upon addition of 300 ml of dry ether a white solid separated. It was allowed to settle. The solution was decanted off and the solid washed with two 150 ml portions of ether, dried on a rotary evaporator and dissolved in 120 ml of dry pyridine. 5.73 ml (0.044 mol) of propionic anhydride were added and the mixture was stirred at room temperature for 1 hour and then evaporated. The residue was dissolved in 250 ml of chloroform and the solution washed with 100 ml of 1-N hydrochloric acid, 100 ml of water and 100 ml of 5% sodium bicarbonate solution, dried over magnesium sulphate and evaporated to an oil. This oil crystallised from ethyl acetate/ether to yield 3.5 g of N-propionyl-L-alanyl-L-proline anilide. A second crop (1.5 g) was obtained from the mother liquor on allowing same to stand. The two crops were combined and chromatographed on 200 g of silica gel. 2% methanol/chloroform was used for the elution and 15 ml fractions were collected. Fractions 35-90 were combined and evaporated. The residue was recrystallised from ethyl acetate/petroleum ether to give 3.24 g (46%) of N-propionyl-L-alanyl-L-proline anilide of melting point 156°-157° C.; [α]D20 =-188.7° (c=1.034% in methanol).

Workup

  1. customseparated
  2. customThe solution was decanted off
  3. washthe solid washed with two 150 ml portions of ether
  4. customdried on a rotary evaporator
  5. dissolutiondissolved in 120 ml of dry pyridine
  6. stirringthe mixture was stirred at room temperature for 1 hour
  7. customevaporated
  8. dissolutionThe residue was dissolved in 250 ml of chloroform
  9. washthe solution washed with 100 ml of 1-N hydrochloric acid, 100 ml of water and 100 ml of 5% sodium bicarbonate solution
  10. dry with materialdried over magnesium sulphate
  11. customevaporated to an oil
  12. customThis oil crystallised from ethyl acetate/ether

Sources & evidence

ORD record
ord-9463e9fe92bb470daedd28d86d10f171
Source dataset
uspto-grants-1980_02
Patent number
US04187216

Reaction notes

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