4-Methylmorpholine → HCID 15021428, compound

HRID 1461620Notes

Reaction equation

HRID 1461620 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C@H:9]([C:17]([NH:19][C@H:20]([C:25]([O:27][CH3:28])=[O:26])[CH2:21][CH:22]([CH3:24])[CH3:23])=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CN1CCOCC1.[OH:36][C:37]([CH3:42])([CH3:41])[C:38](=O)[CH3:39].[BH3-]C#N.[Na+]>CO>[CH3:28][O:27][C:25](=[O:26])[C@H:20]([CH2:21][CH:22]([CH3:24])[CH3:23])[NH:19][C:17](=[O:18])[C@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[NH:8][CH:38]([CH3:39])[C:37]([OH:36])([CH3:42])[CH3:41]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 82613-Hydroxy-3-methyl-2-butanoneHCID 5003444Sodium cyanoborohydrideHCID 131716912HCID 131716912, compound

Product 1

HCID 15021428HCID 15021428, compoundYield 80.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of TFA-Phe-Leu-OMe (0.56 mmol) in MeOH was added N-methylmorpholine (0.93 mL, pH=7), 3-hydroxy-3-methyl-2-butanone (0.84 mmol), and NaCNBH3 (0.72 mmol) under a N2 atmosphere. The reaction mixture was stirred overnight at room temperature and quenched with 50 mL of saturated NaHCO3. The aqueous layer was extracted 3 times with EtOAc (25 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, concentrated, and then flash chromatographed (1-3% MeOH/CH2Cl2 ; SiO2 gel) to yield 0.17 g (80% yield) of N-(2-hydroxy-2-methyl-1-methylpropyl)-L-phenylalanyl-L-leucine methyl ester as an oil.

Workup

  1. customquenched with 50 mL of saturated NaHCO3
  2. extractionThe aqueous layer was extracted 3 times with EtOAc (25 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customflash chromatographed (1-3% MeOH/CH2Cl2 ; SiO2 gel)

Sources & evidence

ORD record
ord-fc96348f0d844aabbf0fd4bb3b1a96f6
Source dataset
uspto-grants-1991_12
Patent number
US05075451

Reaction notes

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