Sodium hydride → HCID 67999255, compound

HRID 931909Notes

Reaction equation

HRID 931909 reaction equation
[C:1](CP(=O)(OCC)OCC)#[N:2].[CH3:12]N1C(=O)N(C)CCC1.[H-].[Na+].[Cl:23][C:24]1[CH:25]=[C:26]([C@@H:30]2[C@@H:35]([C:36]3[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=3)[N:34]([C@@H:43]([CH2:46][CH3:47])[CH:44]=O)[C:33](=[O:48])[C@@H:32]([CH2:49][C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:31]2)[CH:27]=[CH:28][CH:29]=1>C1COCC1>[Cl:23][C:24]1[CH:25]=[C:26]([C@@H:30]2[C@@H:35]([C:36]3[CH:37]=[CH:38][C:39]([Cl:42])=[CH:40][CH:41]=3)[N:34]([C@@H:43]([CH2:44][CH3:12])[CH:46]=[CH:47][C:1]#[N:2])[C:33](=[O:48])[C@@H:32]([CH2:49][C:50]([O:52][C:53]([CH3:56])([CH3:54])[CH3:55])=[O:51])[CH2:31]2)[CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 86660717HCID 86660717, compound

Product 1

HCID 67999255HCID 67999255, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of diethyl cyanomethylphosphonate (62.4 μL, 0.396 mmol) and DMPU (239 μL, 1.98 mmol) in THF (661 μL) was added 60% sodium hydride a s asuspension in mineral oil (11.89 mg, 0.297 mmol) at 0° C. The mixture was stirred for 30 min, and then treated with a solution of 100 mg (0.2 mmol) of tert-butyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxo-1-((R)-1-oxobutan-2-yl)piperidin-3-yl)acetate (Example 21, Step C) in THF (661 μL). After being stirred for 12 h, the reaction was quenched with water, extracted (2×EtOAc) and the combined organic layers were washed with sat. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by flash chromatography on silica gel (10 to 20% EtOAc/Hex, a gradient elution) provided the of the title compound as a mixture of E- and Z-isomers.

Workup

  1. stirringAfter being stirred for 12 h
  2. customthe reaction was quenched with water
  3. extractionextracted (2×EtOAc)
  4. washthe combined organic layers were washed with sat. NaCl solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customPurification of the residue by flash chromatography on silica gel (10 to 20% EtOAc/Hex
  9. washa gradient elution)

Sources & evidence

ORD record
ord-02b50e2f30814d5cb8a1da3d30c4d3db
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

Loading…