4-Methylmorpholine → N-(Toluene-4-sulfonyl)-L-alanyl-L-phenylalanine Benzyl Ester

HRID 411266Notes

Reaction equation

HRID 411266 reaction equation
[C:1]1([CH3:16])[CH:6]=[CH:5][C:4]([S:7]([NH:10][C@H:11]([C:13]([OH:15])=O)[CH3:12])(=[O:9])=[O:8])=[CH:3][CH:2]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1.[CH2:51]([O:58][C:59](=[O:69])[C@H:60]([CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[NH2:61])[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>CN(C=O)C>[CH2:51]([O:58][C:59](=[O:69])[C@H:60]([CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[NH:61][C:13](=[O:15])[C@H:11]([CH3:12])[NH:10][S:7]([C:4]1[CH:3]=[CH:2][C:1]([CH3:16])=[CH:6][CH:5]=1)(=[O:8])=[O:9])[C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 736312Benzyl 3-phenyl-L-alaninateHCID 737622N-Tosyl-L-alanine

Product 1

HCID 53937992N-(Toluene-4-sulfonyl)-L-alanyl-L-phenylalanine Benzyl EsterYield 40.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To N-(toluene-4-sulfonyl)-L-alanine (2.0 mmoles) in DMF (10 mL) was added BOP (2.1 mmoles) and N-methylmorpholine (4.0 mmoles) and the reaction stirred at room temperature for 45 minutes. L-Phenylalanine benzyl ester (2.0 mmoles) was added and the reaction stirred for 16 hours at room temperature. The reaction mixture was extracted with water (100 mL) and diethyl ether (3×50 mL) The combined organic layers were successively washed with 0.2 N HCl (2×50 mL), sat. NaHCO3 (50 mL), and sat. NaCl (50 mL). The organic layer was dried over MgSO4, filtered, and concentrated to yield a colorless oil (387 mg, 40%). The crude product was purified by silica gel chromatography (50% EtOAc /Hexane, Rf=0.61). The title compound was crystalized from CHCl3/Hexane to yield a white solid, mp=109-110° C.

Workup

  1. stirringthe reaction stirred for 16 hours at room temperature
  2. extractionThe reaction mixture was extracted with water (100 mL) and diethyl ether (3×50 mL) The combined organic layers
  3. washwere successively washed with 0.2 N HCl (2×50 mL), sat. NaHCO3 (50 mL), and sat. NaCl (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ad725e2be6674f7db449e0af3efe9b03
Source dataset
uspto-grants-2003_05
Patent number
US06559127B1

Reaction notes

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