Sodium hydride → HCID 131734821, compound

HRID 1778507Notes

Reaction equation

HRID 1778507 reaction equation
[H-].[Na+].[C:3]([CH2:5]P(=O)(OCC)OCC)#[N:4].[CH2:14]([N:21]1[CH:26]2[CH:27]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH2:28][CH:22]1[CH2:23][C:24](=O)[CH2:25]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O1CCCC1>[CH2:14]([N:21]1[CH:26]2[CH:27]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH2:28][CH:22]1[CH2:23]/[C:24](=[CH:5]\[C:3]#[N:4])/[CH2:25]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 21699649HCID 21699649, compound

Product 1

HCID 131734821HCID 131734821, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (6.98 g, 173 mmol) in tetrahydrofuran (460 mL) at 0° C. was added dropwise a solution of diethyl cyanomethylphosphonate (18.5 mL, 103.8 mmol) in tetrahydrofuran (80 mL). The reaction was refluxed for 1 hour and then cooled at 0° C. again. To the reaction mixture was added a solution of compound 86a (26.0 g, 75 mol) in tetrahydrofuran (80 mL). The reaction was allowed to warm up to room temperature and stirred 2 hours. The reaction mixture was then quenched with saturated aqueous solution of NaHCO3, and most of the THF was removed under reduced pressure. Ethyl acetate (200 mL) was added, washed with water, brine, dried over Na2SO4 and evaporated to dryness. The residue was purified on silica gel, eluting with 0 to 20% EtOAc in hexanes, to give the desired product (2E)-2-[8-benzyl-6-[tert-butyl(dimethyl)silyl]oxy-8-azabicyclo[3.2.1]octan-3-ylidene]acetonitrile 86b (27 g, 98%). MS: calc'd (MH+) 369, measured (MH+) 369.

Workup

  1. temperatureThe reaction was refluxed for 1 hour
  2. temperatureto warm up to room temperature
  3. customThe reaction mixture was then quenched with saturated aqueous solution of NaHCO3
  4. custommost of the THF was removed under reduced pressure
  5. additionEthyl acetate (200 mL) was added
  6. washwashed with water, brine
  7. dry with materialdried over Na2SO4
  8. customevaporated to dryness
  9. customThe residue was purified on silica gel
  10. washeluting with 0 to 20% EtOAc in hexanes

Sources & evidence

ORD record
ord-86d96bb1e40b4ef3910fc6b98d5995cb
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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