Dimethylformamide → HCID 22499493, compound

HRID 929959Notes

Reaction equation

HRID 929959 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.Cl[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([CH3:24])[C:19]=1C#N.C[N:28](C=O)C>>[C:24]([C:20]1[CH:19]=[C:18]([O:3][CH:4]2[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:9]2)[CH:23]=[CH:22][N:21]=1)#[N:28]

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 67125855HCID 67125855, compound

Product 1

HCID 22499493HCID 22499493, compoundYield 71%

Procedure

NaH (60% in mineral oil, 303 mg, 7.6 mmol) in 15 mL of DMF was stirred at rt in a round-bottom flask. tert-Butyl 4-hydroxypiperidine-1-carboxylate (1.42 g, 7.0 mmol) was added in portions and the resulting mixture was stirred at rt for 30 min. 4-Chlorocyanopicoline (750 mg, 5.4 mmol) in 5 mL of DMF was added dropwise. After stirring at rt for 1 h, LC-MS indicated that the reaction was complete. The reaction mixture was then partitioned between EtOAc (30 mL) and water (25 mL). The organic layer was washed with brine (10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give an oil which was purified by silica gel flash chromatography, eluting with 0-20% EtOAc in hexanes, to give tert-butyl 4-(2-cyanopyridin-4-yloxy)piperidine-1-carboxylate (1.2 g, 71%) as a light yellow oil. LC-MS (ESI) m/z 304 (M+H)+.

Workup

  1. stirringAfter stirring at rt for 1 h
  2. customThe reaction mixture was then partitioned between EtOAc (30 mL) and water (25 mL)
  3. washThe organic layer was washed with brine (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give an oil which
  8. customwas purified by silica gel flash chromatography
  9. washeluting with 0-20% EtOAc in hexanes

Sources & evidence

ORD record
ord-43983ebb78a447eba8d8d38b55f9251e
Source dataset
uspto-grants-2016_03
Patent number
US09296722B2

Reaction notes

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