4-Methylmorpholine → Tert-butyl N-[(3S)-1-bromo-5-methyl-2-oxohexan-3-YL]carbamate

HRID 393562

Reaction equation

HRID 393562 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:17]N1CCOCC1.ClCCOC=O.[N+](=C)=[N-].[BrH:33].C(O)(=O)C>O1CCCC1.C(OCC)C.O>[Br:33][CH2:17][C:10](=[O:12])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH:14]([CH3:16])[CH3:15]

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 9550DiazomethaneHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 2467482-Chloroethyl formateHCID 21893785Acetic Acid Mixture with Hydrobromic Acid

Product 1

HCID 11034179Tert-butyl N-[(3S)-1-bromo-5-methyl-2-oxohexan-3-YL]carbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under atmosphere of argon, to a solution of (2S)-2-(t-butoxycarbonylamino)-4-methylpentanoic acid (t-butoxycarbonyl-L-leucine) (37.4 g) in tetrahydrofuran (800 ml) was added N-methylmorpholine (33 ml) at −25° C. and the mixture was stirred for 10 minutes. To the mixture was added chloroethylformate (15.8 ml) and the mixture was stirred for 20 minutes. Thereto was added a solution of diazomethane in diethyl ether and the mixture was stirred for another 2 hours. Thereto was added a mixture of 47% hydrobromic acid-acetic acid (1:1) at 0° C. and the mixture was stirred for 15 minutes. To the reaction mixture was added water and was extracted with a mixture of ethyl acetate-hexane. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate and was concentrated. The residue was washed with cooled hexane to give the title compound (27.4 g) having the following physical data.

Workup

  1. stirringthe mixture was stirred for 20 minutes
  2. stirringthe mixture was stirred for another 2 hours
  3. additionThereto was added
  4. stirringthe mixture was stirred for 15 minutes
  5. extractionwas extracted with a mixture of ethyl acetate-hexane
  6. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate
  7. dry with materiala saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate
  8. concentrationwas concentrated
  9. washThe residue was washed with cooled hexane

Sources & evidence

ORD record
ord-a70f5ebccb964f229b26a4b36f6d4754
Source dataset
uspto-grants-2004_10
Patent number
US06809092B2

Linked notes

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