Potassium Iodide → 6-[2-[4-[(4-fluorophenyl)hydroxymethyl]-1-piperidinyl]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one

HRID 325929Notes

Reaction equation

HRID 325929 reaction equation
Br[CH2:2][CH2:3][C:4]1[C:9](=[O:10])[N:8]2[CH2:11][CH2:12][S:13][C:7]2=[N:6][C:5]=1[CH3:14].[F:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[OH:23])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>CC(C)CC(=O)C>[F:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]([OH:23])[CH:24]2[CH2:29][CH2:28][N:27]([CH2:2][CH2:3][C:4]3[C:9](=[O:10])[N:8]4[CH2:11][CH2:12][S:13][C:7]4=[N:6][C:5]=3[CH3:14])[CH2:26][CH2:25]2)=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 4778266(4-Fluorophenyl)(piperidin-4-yl)methanolHCID 155864636-(2-bromoethyl)-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one

Product 1

HCID 155864366-[2-[4-[(4-fluorophenyl)hydroxymethyl]-1-piperidinyl]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-oneYield 42%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 6.8 parts of 6-(2-bromoethyl)-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one, 3.15 parts of α-(4-fluorophenyl)-4-piperidinemethanol, 4.8 parts of sodium carbonate, 0.1 parts of potassium iodide and 200 parts of 4-methyl-2-pentanone was stirred and refluxed for 24 hours. The reaction mixture was cooled, washed with 50 parts of water, dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue solidified upon triturating in acetonitrile. The product was filtered off, washed twice with acetonitrile and dried, yielding 2.5 parts (42%) of 6-[2-[4-[(4-fluorophenyl)hydroxymethyl]-1-piperidinyl]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one; mp. 204.3° C. (compound 33).

Workup

  1. temperaturerefluxed for 24 hours
  2. temperatureThe reaction mixture was cooled
  3. washwashed with 50 parts of water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column-chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customupon triturating in acetonitrile
  12. filtrationThe product was filtered off
  13. washwashed twice with acetonitrile
  14. customdried

Sources & evidence

ORD record
ord-9f8ef1219a174f7d90b8627ee61d5bab
Source dataset
uspto-grants-1984_04
Patent number
US04443451

Reaction notes

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