4-Methylmorpholine → Boc-Ala-NH2

HRID 452035Notes

Reaction equation

HRID 452035 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:13])[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:15]1CCOCC1.ClC(OCC(C)C)=O.[OH-].[NH4+]>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH3:13])[C:10]([NH2:15])=[O:11])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 14923Ammonium HydroxideHCID 62365Isobutyl chloroformateHCID 85082Tert-butoxycarbonylalanine

Product 1

HCID 7015295Boc-Ala-NH2

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (2S)-2-[(tert-butoxycarbonyl)amino]propanoic acid (1 g, 0.005 mol) in THF at 0° C. was added 4-methylmorpholine (0.588 g, 0.00581 mol) followed by dropwise addition of isobutyl chloroformate (0.794 g, 0.00581 mol) over 2 min. The reaction was stirred at 0° C. for 30 min. after which a solution of 30 wt. % ammonium hydroxide (12.0 mL, 0.0925 mol) was quickly poured into the reaction. The reaction was warmed to room temperature and stirred for 5 h. The reaction mixture was concentrated. Water was added and the mixture extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to afford the crude product which was directly used in the next step reaction without further purification (800 mg, 80%). 1H-NMR (300 MHz, DMSO-d6): 12.40 (s, 1H), 7.10 (d, J=7.0 Hz, 1H), 3.88 (m, 1H), 1.35 (s, 9H), 1.20 (d, J=7.3 Hz, 3H).

Workup

  1. additionwas quickly poured into the reaction
  2. concentrationThe reaction mixture was concentrated
  3. additionWater was added
  4. extractionthe mixture extracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4d71d77198b044d4bc12a2d6e540e7d0
Source dataset
uspto-grants-2013_07
Patent number
US08487096B2

Reaction notes

Loading…