4-Methylmorpholine → HCID 131723142, compound

HRID 277676Notes

Reaction equation

HRID 277676 reaction equation
[NH:1]([C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[C@H:2]([C:4]([NH:6][C@H:7]([C:9]([NH:11][C@H:12]([C:14](O)=[O:15])[CH3:13])=[O:10])[CH3:8])=[O:5])[CH3:3].CN1CCOCC1.[BH4-].[Na+].C([O-])(O)=O.[Na+]>C1COCC1.CN(C=O)C.O>[NH:1]([C:17]([O:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:18])[C@H:2]([C:4]([NH:6][C@H:7]([C:9]([NH:11][C@H:12]([CH2:14][OH:15])[CH3:13])=[O:10])[CH3:8])=[O:5])[CH3:3]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 14459756N-[(Benzyloxy)carbonyl]-L-alanyl-L-alanyl-L-alanine

Product 1

HCID 131723142HCID 131723142, compoundYield 24.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To 5 g (0.014 mol) of Z-Ala-Ala-AlaOH dissolved in THF/DMF 1:1 (50 mL) at −10° C. under a N2 atmosphere were added 1.6 mL (0.014 mol) NMM and 1.9 mL (0.014 mol) IBCF. The reaction mixture was stirred 15 minutes, filtered, and the filtrate added slowly to an ice-cold solution of NaBH4 (1.4 g, 0.037 mol) in H2O (3 mL) and stirred 1 hour at ice-bath temperature and 1 hour at room temperature. The reaction mixture was cooled to 0° C. and treated with saturated NaHCO3 solution, extracted with EtOAc, washed with 1M HCl that is saturated with NaHCO3, dried over anhydrous MgSO4, and evaporated to dryness. The crude product was purified over a silica gel column eluted with 95:5 EtOAc/MeOH to give 1.2 g product.

Workup

  1. filtrationfiltered
  2. stirringstirred 1 hour at ice-bath temperature and 1 hour at room temperature
  3. extractionextracted with EtOAc
  4. washwashed with 1M HCl that
  5. dry with materialdried over anhydrous MgSO4
  6. customevaporated to dryness
  7. customThe crude product was purified over a silica gel column
  8. washeluted with 95:5 EtOAc/MeOH

Sources & evidence

ORD record
ord-ce4eb2239e484af88531f03b00f1e384
Source dataset
uspto-grants-2002_03
Patent number
US06358928B1

Reaction notes

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