Potassium Iodide → 1-[3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl]-2,3-dihydro-2,2-dimethyl-4(1H)-quinazolinone

HRID 1156355Notes

Reaction equation

HRID 1156355 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8](=[O:15])[NH:7][C:6]1([CH3:17])[CH3:16].Cl.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[O:27])=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>O.CC(C)CC(=O)C>[F:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([CH:28]2[CH2:33][CH2:32][N:31]([CH2:2][CH2:3][CH2:4][N:5]3[C:14]4[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=4)[C:8](=[O:15])[NH:7][C:6]3([CH3:17])[CH3:16])[CH2:30][CH2:29]2)=[O:27])=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 202789421-(3-chloropropyl)-2,3-dihydro-2,2-dimethyl-4(1H)-quinazolinone

Product 1

HCID 128520671-[3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl]-2,3-dihydro-2,2-dimethyl-4(1H)-quinazolinoneYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 5.6 parts of 1-(3-chloropropyl)-2,3-dihydro-2,2-dimethyl-4(1H)-quinazolinone, 4.9 parts of (4-fluorophenyl) (4-piperidinyl)methanone hydrochloride, 10 parts of sodium carbonate, 0.1 parts of potassium iodide and 200 parts of 4-methyl-2-pentanone is stirred and refluxed overnight with water-separator. The reaction mixture is cooled, water is added and the layers are separated. The 4-methyl-2-pentanone phase is dried, filtered and evaporated. The solid residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The solid residue is stirred in 2,2'-oxybispropane. The product is filtered off and dried, yielding 6.6 parts (78%) of 1-[3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl]-2,3-dihydro-2,2-dimethyl-4(1H)-quinazolinone; mp. 185.7° C.

Workup

  1. temperatureThe reaction mixture is cooled
  2. customthe layers are separated
  3. dry with materialThe 4-methyl-2-pentanone phase is dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe solid residue is purified by column-chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  8. customThe pure fractions are collected
  9. customthe eluent is evaporated
  10. stirringThe solid residue is stirred in 2,2'-oxybispropane
  11. filtrationThe product is filtered off
  12. customdried

Sources & evidence

ORD record
ord-2c86ee42cc654b87abe799a80b9d805a
Source dataset
uspto-grants-1982_06
Patent number
US04335127

Reaction notes

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