Ethylmorpholine → N-[(1,1-Dimethylethoxy)carbonyl]-L-alanyl-L-proline phenylmethyl ester

HRID 1263301Notes

Reaction equation

HRID 1263301 reaction equation
[NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].[C:9]([O:13][C:14]([NH:16][C@H:17]([C:19]([OH:21])=O)[CH3:18])=[O:15])([CH3:12])([CH3:11])[CH3:10].ON1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2N=N1.[CH2:32](N1CCOCC1)C>C(OCC)(=O)C.O1CCCC1>[C:9]([O:13][C:14]([NH:16][C@H:17]([C:19]([N:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([O:5][CH2:32][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:4])=[O:21])[CH3:18])=[O:15])([CH3:10])([CH3:11])[CH3:12]

Participants

7

Reactant 4

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 85082Tert-butoxycarbonylalanineHCID 145742L-Proline

Product 1

HCID 13068139N-[(1,1-Dimethylethoxy)carbonyl]-L-alanyl-L-proline phenylmethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6.0 g (0.025 m) of the benzyl ester of L-proline, 4.7 g (0.025 m) of N-tert.-butoxycarbonyl-L-alanine, 6.75 g (0.05 m) of 1-hydroxybenzotriazole, 3.2 ml (2.82 g, 0.025 m) of N-ethylmorpholine and 65 ml of dry tetrahydrofuran was cooled, filtered and added to a mixture of 5.15 g (0.025 m) of dicyclohexylcarbodiimide and 10 ml of tetrahydrofuran. The mixture was stirred at 0° for 30 minutes, then, at 25° for 18 hours. The reaction mixture was filtered. The filtrate was evaporated to give a residue which was dissolved in ethyl acetate. The solution was washed with 1 to 10% acetic acid, water, 5% sodium bicarbonate solution and brine, then, dried over anhydrous magnesium sulfate and concentrated to leave 9.8 g of crude N-tert.-butoxycarbonyl-L-alanyl-L-proline, benzyl ester (the t-boc).

Workup

  1. temperaturewas cooled
  2. filtrationfiltered
  3. additionadded to a mixture of 5.15 g (0.025 m) of dicyclohexylcarbodiimide and 10 ml of tetrahydrofuran
  4. waitat 25° for 18 hours
  5. filtrationThe reaction mixture was filtered
  6. customThe filtrate was evaporated
  7. customto give a residue which
  8. washThe solution was washed with 1 to 10% acetic acid, water, 5% sodium bicarbonate solution and brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-730aec3c4c1d4cd493c1174c060a4d44
Source dataset
uspto-grants-1984_06
Patent number
US04456594

Reaction notes

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