Pyrrolidine → 7-Fluoro-n-methylspiro[2h-1-benzopyran-2,4'-piperidine]-4(3h)one

HRID 479453Notes

Reaction equation

HRID 479453 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[C:4]([OH:11])[CH:3]=1.[CH3:12][N:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1.N1CCCC1>CO.ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8](=[O:10])[CH2:9][C:16]3([O:11][C:4]=2[CH:3]=1)[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][CH2:15]3

Participants

6

Reactant 3

HCID 31268Pyrrolidine2×HCID 740491-Methyl-4-piperidoneHCID 27373264'-Fluoro-2'-hydroxyacetophenone

Product 1

HCID 187709727-Fluoro-n-methylspiro[2h-1-benzopyran-2,4'-piperidine]-4(3h)one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred solution of 4′-fluoro-2′-hydroxyacetophenone (15.97 g), 1-methyl-4-piperidone (12.74 cm3) and pyrrolidine (4.325 cm3) in methyl alcohol (250 cm3) was heated to reflux under nitrogen. After 0.5 h, further pyrrolidine (4.33 cm3) was added and, after another 0.5 h, the solution was allowed to cool. The reaction mixture was then evaporated under reduced pressure to give an oil, which was dissolved in dichloromethane (400 cm3). This solution was washed with water (3×400 cm3), dried (Na2SO4) and evaporated to give an oil (25.7 g). Flash chromatography on silica (eluting with dichloromethane-methyl alcohol-33% aqueous ammonia=380:20:1) gave the purified product as an oil (14.41 g).

Workup

  1. temperatureto reflux under nitrogen
  2. temperatureto cool
  3. customThe reaction mixture was then evaporated under reduced pressure
  4. customto give an oil, which
  5. washThis solution was washed with water (3×400 cm3)
  6. dry with materialdried (Na2SO4)
  7. customevaporated

Sources & evidence

ORD record
ord-cf7252fc7327422b847871bbd1eef5ee
Source dataset
uspto-grants-2003_11
Patent number
US06645973B1

Reaction notes

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