Sodium hydride → HCID 67999255, compound

HRID 1048223Notes

Reaction equation

HRID 1048223 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 as a suspension 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-dd7619caf7b74839a4cd7217b1074ca8
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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