1,2-Dichloroethane → Boc-Phe Morpholinamide

HRID 399509Notes

Reaction equation

HRID 399509 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.C(Cl)CCl.[NH:49]([C:61](OC(C)(C)C)=[O:62])[C@H](C(O)=O)CC1C=CC=CC=1.N1CCOCC1>CN(C)C=O>[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[N:20]1([C:61]([NH2:49])=[O:62])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 81531DiisopropylethylamineHCID 131720327Boc-Phe morpholine

Product 1

HCID 131717846Boc-Phe MorpholinamideYield 99%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 250 ml flask was charged with Boc-Phe-OH (10 g, 38 mmol), morpholine (3.3 g, 38 mmol) and 1-hydroxybenztriazole (5.1 g, 38 mmol) in 100 ml dry dimethylformamide (DMF). To this solution was added diisopropylethylamine (DIEA) at zero degrees C until the pH value reached 8, followed by addition of EDC (8.8 g, 46 mmol). The solution was slowly warmed to room temperature. The mixture was stirred for eight hours at room temperature (about 22° C.). The DMF was removed by vacuum evaporator, ethyl acetate and water were added, and the layers were separated. The aqueous layer was extracted with ethyl acetate (50 ml×2), combined extracts were washed with 1N HCl, saturated NaHCO3, water and brine, dried with MgSO4, filtered and concentrated to give a colorless liquid (12.8 g, 37.7 mmol; 99 percent yield) that was characterized by 1 HNMR as Boc-Phe-morpholine.

Workup

  1. customThe DMF was removed by vacuum evaporator, ethyl acetate and water
  2. additionwere added
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with ethyl acetate (50 ml×2)
  5. washwere washed with 1N HCl, saturated NaHCO3, water and brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a colorless liquid (12.8 g, 37.7 mmol; 99 percent yield) that

Sources & evidence

ORD record
ord-317de26aec934875ae61ea1c1a8ad0e4
Source dataset
uspto-grants-1998_10
Patent number
US05821231

Reaction notes

Loading…