Hexamethylphosphoramide → HCID 57270456, compound

HRID 1078728Notes

Reaction equation

HRID 1078728 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:12])[C:9](=[O:11])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)P(=O)(N(C)C)N(C)C.C([N-]C(C)C)(C)C.[Li+].[C:32]([O:36][C:37]([N:39]1[CH2:45][C@H:44]([O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48])[CH2:43][C@H:40]1[CH:41]=[O:42])=[O:38])([CH3:35])([CH3:34])[CH3:33].[Cl-].[NH4+]>O1CCCC1.O.C(OCC)(=O)C>[C:32]([O:36][C:37]([N:39]1[CH2:45][C@H:44]([O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48])[CH2:43][C@H:40]1[CH:41]([OH:42])[CH2:10][C:9](=[O:11])[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH3:12])=[O:38])([CH3:35])([CH3:34])[CH3:33]

Participants

9

Reactant 5

HCID 12679HexamethylphosphoramideHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateHCID 11052126HCID 11052126, compound

Product 1

HCID 57270456HCID 57270456, compoundYield 37.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

Under a nitrogen atmosphere, a solution of N-tert-butoxycarbonyl-N-methylacetamide (289 mg, 1.67 mmol) in tetrahydrofuran (1.0 ml) and then hexamethylphosphoric triamide (290 μl, 1.67 mmol) were dropwise added at -78° C. to a solution comprising a 2.0M lithium diisopropylamide--tetrahydrofuran solution (835 μl, 1.67 mmol) and tetrahydrofuran (10 ml). The mixture was stirred at -78° C. for 20 minutes, and a solution of (2S,4R)-N-tert-butoxycarbonyl-4-tert-butyldimethylsiloxyprolinal (500 mg, 1.52 mmol) in tetrahydrofuran (2 ml) was dropwise added thereto. The reaction mixture was stirred at the same temperature for 30 minutes. Saturated aqueous ammonium chloride was added to the reaction mixture, and 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 (heptane-ethyl acetate=1:2) to give the title compound (288.8 mg, yield: 37.8%).

Workup

  1. stirringThe reaction mixture was stirred at the same temperature for 30 minutes
  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-7c20d1727c0b4c04a722f4821ac2f737
Source dataset
uspto-grants-1996_08
Patent number
US05550121

Reaction notes

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