4-Methylmorpholine → N-tert.-butoxycarbonyl-beta-alanyl-L-proline amide

HRID 1263304Notes

Reaction equation

HRID 1263304 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH:15]1[CH2:22][CH2:21][CH2:20][C@H:16]1[C:17]([NH2:19])=[O:18].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.O1CCCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([N:15]1[CH2:22][CH2:21][CH2:20][C@H:16]1[C:17]([NH2:19])=[O:18])=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 12707183(S)-Pyrrolidine-2-carboxamide monohydrochloride

Product 1

HCID 22826873N-tert.-butoxycarbonyl-beta-alanyl-L-proline amideYield 33.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6.28 g (0.0332 m) of N-tert.-butoxycarbonyl-β-alanine, 5.0 g (0.0332 m) of L-proline amide hydrochloride, 8.96 g (0.0664 m) of 1-hydroxybenzotriazole, 12 ml of N-methylmorpholine, 75 ml of tetrahydrofuran, 40 ml of dimethylformamide and 6.84 g (0.0332 m) of dicyclohexylcarbodiimide was stirred at 25° for 17 hours. The solvents were evaporated in vacuo and the residue dissolved in ethyl acetate and water. The separated organic layer was washed with small volumes of dilute hydrochloric acid, brine, 5% bicarbonate and brine. The dried extract was concentrated to give 3.2 g of syrupy N-tert.-butoxycarbonyl-β-alanyl-L-proline amide. The methane chemical ionization mass spectrum was in agreement with the dipeptide structure.

Workup

  1. customThe solvents were evaporated in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate
  3. washThe separated organic layer was washed with small volumes of dilute hydrochloric acid, brine, 5% bicarbonate and brine
  4. extractionThe dried extract
  5. concentrationwas concentrated

Sources & evidence

ORD record
ord-697f7490826e4b24bbf43388f926f328
Source dataset
uspto-grants-1984_06
Patent number
US04456594

Reaction notes

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