N-Methylacetamide → HCID 22865001, compound

HRID 1078727Notes

Reaction equation

HRID 1078727 reaction equation
[CH3:1][NH:2][C:3](=[O:5])[CH3:4].CN(C)P(=O)(N(C)C)N(C)C.C([N-]C(C)C)(C)C.[Li+].[C:25]([O:29][C:30]([N:32]1[CH2:38][C@H:37]([O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])[CH2:36][C@H:33]1[CH:34]=[O:35])=[O:31])([CH3:28])([CH3:27])[CH3:26]>O1CCCC1.C(OCC)(=O)C.O.O>[C:25]([O:29][C:30]([N:32]1[CH2:38][C@H:37]([O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])[CH2:36][C@H:33]1[CH:34]([OH:35])[CH2:4][C:3](=[O:5])[NH:2][CH3:1])=[O:31])([CH3:28])([CH3:27])[CH3:26]

Participants

8

Reactant 4

HCID 6582N-MethylacetamideHCID 12679HexamethylphosphoramideHCID 2724682Lithium diisopropylamideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylate

Product 1

HCID 22865001HCID 22865001, compoundYield 25.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×HCID 22728543Water ethylacetateSolvent

Conditions

Temperature
-78 °C

Procedure

Under a nitrogen atmosphere, a solution of N-methylacetamide (116 μl, 1.52 mmol) in tetrahydrofuran (2 ml) and then hexamethylphosphoric triamide (555 μl, 3.19 mmol) were dropwise added at -78° C. to a solution comprising 2.0M lithium diisopropylamide--tetrahydrofuran (1.6 ml, 3.19 mmol) and tetrahydrofuran (10 ml). The mixture was stirred at -78° C. for 30 minutes. Then, a solution of (2S,4R)-N-tert-butoxycarbonyl-4-tert-butyldimethylsiloxyprolinal (500 mg, 1.52 mmol) in tetrahydrofuran (2 ml) was dropwise added. The reaction mixture was stirred at room temperature for 2 h. Water was added to the reaction mixture. Then, the reaction mixture was poured into a mixture of ethyl acetate-water. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained oily residue was subjected to silica gel column chromatography (chloroform--methanol=20:1) to give the title compound (158 mg, yield: 25.9%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2 h
  2. washThe organic layer was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1a583f2c104e472e8c9468e673d17c71
Source dataset
uspto-grants-1996_08
Patent number
US05550121

Reaction notes

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