Sodium hydride → {4-[(R)-2-(1-ethoxy-ethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetonitrile

HRID 2052973Notes

Reaction equation

HRID 2052973 reaction equation
[H-].[Na+].[CH2:3]([O:5][CH:6]([O:8][CH2:9][C@@H:10]1[NH:15][C:14](=[O:16])[CH2:13][CH2:12][CH2:11]1)[CH3:7])[CH3:4].I[CH2:18][C:19]#[C:20][CH2:21][O:22][CH2:23][C:24]#[N:25].[NH4+].[Cl-]>CN(C=O)C>[CH2:3]([O:5][CH:6]([O:8][CH2:9][C@H:10]1[CH2:11][CH2:12][CH2:13][C:14](=[O:16])[N:15]1[CH2:18][C:19]#[C:20][CH2:21][O:22][CH2:23][C:24]#[N:25])[CH3:7])[CH3:4]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 58961293(R)-6-(1-ethoxyethoxymethyl)-piperidin-2-oneHCID 86012516(4-Iodo-but-2-ynyloxy)-acetonitrile

Product 1

HCID 69021582{4-[(R)-2-(1-ethoxy-ethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetonitrileYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% dispersion in oil, 600 mg, 15.0 mmol) was added to a solution of (R)-6-(1-ethoxyethoxymethyl)-piperidin-2-one (from example 50, step 1, 3.00 g, 14.9 mmol) in DMF (20 mL) at 0° C. After 1 h at 0° C., (4-iodo-but-2-ynyloxy)-acetonitrile (3.50 g, 14.9 mmol) in DMF (10 mL) was added via cannula and the reaction was allowed to warm to rt. After 16.5 h at rt, the reaction was treated with saturated aqueous NH4Cl (100 mL) and extracted with EtOAc (3×100 mL). The combined extracts were washed with water (2×100 mL) and brine (2×100 mL) then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→50% EtOAc/CH2Cl2, gradient) afforded 1.83 g (40%) of {4-[(R)-2-(1-ethoxy-ethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetonitrile.

Workup

  1. waitAfter 16.5 h at rt
  2. extractionextracted with EtOAc (3×100 mL)
  3. washThe combined extracts were washed with water (2×100 mL) and brine (2×100 mL)
  4. dry with materialthen dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→50% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-ace25044ea464c2aab49e0abb8d8336d
Source dataset
uspto-grants-2008_02
Patent number
US07326716B2

Reaction notes

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