4-Fluoroaniline → Despropionyl N-benzyl p-fluoro norfentanyl

HRID 1493870Notes

Reaction equation

HRID 1493870 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.C([BH3-])#N.[Na+].[OH-].[Na+]>C1(C)C=CC=CC=1.CO.[Cl-].[Zn+2].[Cl-].O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:20][C:19]2[CH:21]=[CH:22][C:16]([F:15])=[CH:17][CH:18]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 97314-FluoroanilineHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 51700761-Benzyl-2-piperidone

Product 1

HCID 5109634Despropionyl N-benzyl p-fluoro norfentanylYield 93.2%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Benzylpiperidone (2 g), dissolved in toluene (10 cc), is stirred under argon for 48 hours at room temperature in the presence of 4-fluoroaniline (1.4 g) and 5 Å molecular sieve (4 g). After filtration and concentration to dryness under reduced pressure (5.2 kPa), yellow crystals are obtained, which are then dissolved in methanol (30 cc). This solution is then added to a solution, cooled to 0°-5° C., of sodium cyanoborohydride (1.34 g) and zinc chloride (1.4 g) in methanol (20 cc). After 20 hours at room temperature, the product is taken up with 10N sodium hydroxide solution (5 cc) and with water (20 cc) and the mixture is heated to reflux for 1 hour. The mixture is filtered through a sinter and the filtrate is extracted twice with dichloromethane (100 cc). The organic phase is then dried over magnesium sulphate and thereafter concentrated to dryness under reduced pressure (5.2 kPa). N-Benzyl-4-(4-fluoroanilino)piperidine (2.8 g) is thereby obtained in the form of a whitish powder, m.p. 84° C.

Workup

  1. filtrationAfter filtration and concentration to dryness under reduced pressure (5.2 kPa), yellow crystals
  2. customare obtained
  3. additionThis solution is then added to a solution
  4. temperaturethe mixture is heated
  5. temperatureto reflux for 1 hour
  6. filtrationThe mixture is filtered through a sinter
  7. extractionthe filtrate is extracted twice with dichloromethane (100 cc)
  8. dry with materialThe organic phase is then dried over magnesium sulphate
  9. concentrationconcentrated to dryness under reduced pressure (5.2 kPa)

Sources & evidence

ORD record
ord-4aea5102be554044a70fc7463c21ea62
Source dataset
uspto-grants-1991_06
Patent number
US05025013

Reaction notes

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