Formaldehyde → 4-[2-(1-piperidinyl)-1,1-dimethylethyl]pyridine

HRID 494016Notes

Reaction equation

HRID 494016 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=1)([CH3:3])[CH3:2].Cl.[NH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.[CH2:17]=O>C(O)C>[N:11]1([CH2:2][C:1]([C:4]2[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=2)([CH3:17])[CH3:3])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 696744-IsopropylpyridineHCID 2723721Piperidine, hydrochloride (1:1)

Product 1

HCID 109984984-[2-(1-piperidinyl)-1,1-dimethylethyl]pyridineYield 17%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of 70 g (0.58 M) of 4-isopropylpyridine, 250 g (2 M) of piperidine hydrochloride and 85 g of paraformaldehyde in 600 ml of 95% ethanol is held under reflux for 48 hours. The reaction mixture is then concentrated under reduced pressure and the residue is taken up with 650 ml of 3N sodium hydroxide and extracted with thrice 250 ml of ethyl acetate. The combined organic phases are washed with a solution of sodium chloride, dried and concentrated under reduced pressure. The crude product is distilled under a vacuum of 1 mm Hg and the fraction collected between 80 and 125° C. is purified by silica gel chromatography in eluting with the aid of a toluene/isopropanol mixture (9/1; v/v). 21.4 g of the compound sought after are thus obtained as a clear yellow oil (yield=17%).

Workup

  1. temperatureunder reflux for 48 hours
  2. concentrationThe reaction mixture is then concentrated under reduced pressure
  3. extractionextracted with thrice 250 ml of ethyl acetate
  4. washThe combined organic phases are washed with a solution of sodium chloride
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. distillationThe crude product is distilled under a vacuum of 1 mm Hg
  8. customthe fraction collected between 80 and 125° C.
  9. customis purified by silica gel chromatography
  10. washin eluting with the aid of a toluene/isopropanol mixture (9/1; v/v)

Sources & evidence

ORD record
ord-a740091682a84bff9cbe2afc6220cedc
Source dataset
uspto-grants-2009_05
Patent number
US07538111B2

Reaction notes

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