Sodium hydride → HCID 67999562, compound

HRID 1048410Notes

Reaction equation

HRID 1048410 reaction equation
[C:1]([CH2:3]P(=O)(OCC)OCC)#[N:2].CN1C(=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@:32]([CH2:50][CH:51]3[CH2:55][O:54][C:53]([CH3:57])([CH3:56])[O:52]3)([CH3:49])[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]([CH2:46][CH3:47])[CH:44]=[CH:3][C:1]#[N:2])[C:33](=[O:48])[C@:32]([CH2:50][CH:51]3[CH2:55][O:54][C:53]([CH3:57])([CH3:56])[O:52]3)([CH3:49])[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 58573899HCID 58573899, compound

Product 1

HCID 67999562HCID 67999562, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of diethyl cyanomethylphosphonate (126 μL, 0.799 mmol) and DMPU (481 μL, 3.99 mmol) in THF (1.33 mL) was added 60% sodium hydride in mineral oil (24.0 mg, 0.599 mmol) at 0° C. The mixture was stirred for 30 min, and then treated with a solution of (2S)-2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-3-methyl-2-oxopiperidin-1-yl)butanal prepared above in Step D (207 mg, 0.399 mmol) in THF (1.33 mL). After being stirred for 4 h, the reaction was quenched (water), extracted (2×EtOAc), and washed (sat. aq. NaCl solution). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification of the residue by chromatography on silica gel (24 g SiO2, 30 to 40% EtOAc/Hex, gradient elution) provided the title compound as a colorless liquid.

Workup

  1. stirringAfter being stirred for 4 h
  2. customthe reaction was quenched (water)
  3. extractionextracted (2×EtOAc)
  4. washwashed (sat. aq. NaCl solution)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the residue by chromatography on silica gel (24 g SiO2, 30 to 40% EtOAc/Hex, gradient elution)

Sources & evidence

ORD record
ord-29741fd5dff54b48ab0111714d84c23d
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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