4-Methylmorpholine → N-Cbz-5-hydroxy-L-norvaline methyl ester

HRID 1896157Notes

Reaction equation

HRID 1896157 reaction equation
[NH:1]([C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[C@H:2]([C:8]([O:10][CH3:11])=[O:9])[CH2:3][CH2:4][C:5](=O)[OH:6].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.CO>[CH3:11][O:10][C:8](=[O:9])[C@@H:2]([NH:1][C:12]([O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:13])[CH2:3][CH2:4][CH2:5][OH:6]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2733408(4S)-4-{[(benzyloxy)carbonyl]amino}-5-methoxy-5-oxopentanoic acidHCID 4311764Sodium borohydride

Product 1

HCID 10588891N-Cbz-5-hydroxy-L-norvaline methyl esterYield 105%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

To a cold (−15° C.) solution of Z-Glu-OMe (1.5 g) in THF (70 mL) was added N-methylmorpholine (0.616 mL) followed by isobutyl chloroformate (0.731 mL) dropwise. After 30 min stirring at −15° C., NaBH4 (576 mg) was added, followed MeOH dropwise. The reaction mixture was stirred at −10° C. for 15 min and quenched by the addition of 1M KHSO4 solution. The mixture was extracted with EA. The org. phase was washed with water, dried (Na2SO4) and evaporated off to give 1.5 g of the crude product as colorless oil.

Workup

  1. stirringThe reaction mixture was stirred at −10° C. for 15 min
  2. customquenched by the addition of 1M KHSO4 solution
  3. extractionThe mixture was extracted with EA
  4. washphase was washed with water
  5. dry with materialdried (Na2SO4)
  6. customevaporated off

Sources & evidence

ORD record
ord-13167304eb584463a470cc8ba1f295b5
Source dataset
uspto-grants-2013_08
Patent number
US08518912B2

Reaction notes

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