4-Methylmorpholine → tert-butyl N-[(2S)-1-hydroxy-3-methylbutan-2-yl]carbamate

HRID 277677Notes

Reaction equation

HRID 277677 reaction equation
[C:1]([NH:8][C@H:9]([C:13](O)=[O:14])[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.[BH4-].[Na+].C([O-])(O)=O.[Na+]>C1COCC1.O>[NH:8]([C:1]([O:3][C:4]([CH3:6])([CH3:5])[CH3:7])=[O:2])[C@H:9]([CH2:13][OH:14])[CH:10]([CH3:11])[CH3:12]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 83693Boc-L-ValineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydride

Product 1

HCID 7021464tert-butyl N-[(2S)-1-hydroxy-3-methylbutan-2-yl]carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To 5 g (0.023 mol) of Boc-Valine dissolved in THF (30 mL) at −10° C. under N2 are added NMM (2.5 mL 0.023 mol) and IBCF (3 mL, 0.023 mol). The reaction mixture is stirred 15 minutes and filtered. The filtrate is added slowly to an ice-cold solution of NaBH4 (2.3 g, 0.061 mol) in H2O (10 mL) and stirred 1 hour at ice-bath temperature then 1 hour at room temperature. The reaction mixture is cooled to 0° C. and treated with saturated NaHCO3 solution, extracted with EtOAc, washed with 1M HCl saturated with NaHCO3, dried over anhydrous MgSO4, and evaporated to dryness. The crude Boc-ValCH2OH product is purified over a silica gel column eluted with 95:5 EtOAc/MeOH.

Workup

  1. filtrationfiltered
  2. stirringstirred 1 hour at ice-bath temperature
  3. custom1 hour
  4. customat room temperature
  5. extractionextracted with EtOAc
  6. washwashed with 1M HCl saturated with NaHCO3
  7. dry with materialdried over anhydrous MgSO4
  8. customevaporated to dryness
  9. customThe crude Boc-ValCH2OH product is purified over a silica gel column
  10. washeluted with 95:5 EtOAc/MeOH

Sources & evidence

ORD record
ord-fa916a9574a14c058340cd4147ce6fb7
Source dataset
uspto-grants-2002_03
Patent number
US06358928B1

Reaction notes

Loading…