Ammonia → BOC-Norleucine Amide

HRID 861307Notes

Reaction equation

HRID 861307 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7](O)=[O:8])[CH2:3][CH2:4][CH2:5][CH3:6].C[N:18]1CCOCC1.ClC(OCC(C)C)=O.N.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([NH2:18])=[O:8])[CH2:3][CH2:4][CH2:5][CH3:6]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 311Citric AcidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2733747N-tert-Butoxycarbonyl-L-norleucine

Product 1

HCID 15609364BOC-Norleucine AmideYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N-Boc-L-Nle-OH (0.5 g, 2.2 mmol) in anhydrous THF (15 mL) under Ar at -23° C. was added 4-methylmorpholine followed by iso-butyl chloroformate (0.21 mL, 2.2 mmol). The reaction mixture was then treated with gaseous NH3 for 1 h. Stirring was continued at -23° C. for an additional 2 h. The mixture was warmed to R.T. and then poured onto 10% aqueous citric acid (20 mL). The mixture was extracted with EA (3×50 mL). The combined organics were washed with sat. NaHCO3 (3×25 mL), sat. NaCl (2×25 mL), dried (MgSO4), filtered and concentrated to afford N-Boc-L-Nle-NH2 as a white solid (0.48 g, 91%): 1H NMR (CDCl3, 300 MHz) δ 0.84-0.92 (m, 3H), 1.22-1.31 (m, 4H), 1.41 (s, 9H), 1.49-1.59 (m, 1H), 1.74-2.01 (m, 1H), 4.03-4.1 (m, 1H), 5.06 (d, 1H), 5.75 (s, 1H), 6.25 (s, 1H) ppm.

Workup

  1. extractionThe mixture was extracted with EA (3×50 mL)
  2. washThe combined organics were washed with sat. NaHCO3 (3×25 mL), sat. NaCl (2×25 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7ced5e3f2576450285a63abd736a3e43
Source dataset
uspto-grants-1998_02
Patent number
US05714471

Reaction notes

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