2,6-Dichloropyridine → HCID 57893742, compound

HRID 1822003Notes

Reaction equation

HRID 1822003 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][C:9]1([CH3:16])[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22](Cl)[N:21]=1>CN(C)C=O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([Cl:19])[N:21]=2)[CH2:10][C:9]1([CH3:16])[CH3:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 169892,6-DichloropyridineHCID 24758Sodium hydrideHCID 140285381-Benzyl-2,2-dimethylpiperidin-4-ol

Product 1

HCID 57893742HCID 57893742, compoundYield 38.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Combine 1-benzyl-2,2-dimethyl-piperidin-4-ol (preparation 9) 1.08 g, 4.92 mmol), N,N-dimethylformamide (20 mL) and 95% sodium hydride (0.12 g, 4.92 mmol) and stir. After 30 min., add 2,6-dichloropyridine (0.67 g, 4.52 mmol), stir and heat at 120° C. After 18 hr., cool to ambient temperature and partition between water (100 mL) and ethyl acetate (100 mL). Separate the organic layer and wash the aqueous layer with ethyl acetate (2×100 mL). Combine the organic layers, wash with water (5×100 mL), wash with aqueous NaCl solution, dry over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 9:1 hexane:ethyl acetate to obtain of the title compound (0.57 g, 38%). Mass spectrum (electrospray): m/z=331.1 (M+1); 1H NMR (CDCl3): 7.5 (dd, 1H), 7.3 (m, 5H), 6.8 (d, 1H), 6.6 (d, 1H), 5.2 (m, 1H), 3.9 (d, 1H), 3.2 (d, 1H), 2.65 (m, 1H), 2.4 (m, 1H), 2.0 (m, 2H), 1.7 (m, 1H), 1.6 (m, 1H), 1.3 (s, 3H), 1.2 (s, 3H).

Workup

  1. waitAfter 18 hr
  2. temperature, cool to ambient temperature
  3. custompartition between water (100 mL) and ethyl acetate (100 mL)
  4. customSeparate the organic layer
  5. washwash the aqueous layer with ethyl acetate (2×100 mL)
  6. washCombine the organic layers, wash with water (5×100 mL)
  7. washwash with aqueous NaCl solution
  8. dry with materialdry over sodium sulfate
  9. filtrationfilter
  10. concentrationconcentrate
  11. customPurify the residue by silica gel flash chromatography
  12. washeluting with 9:1 hexane

Sources & evidence

ORD record
ord-574dc430b56b43dfb484b866057a565d
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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