Triethylamine → N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]acetamide

HRID 2294980Notes

Reaction equation

HRID 2294980 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1.Cl.[CH3:14][C:15]1([NH:21][C:22](=[O:24])[CH3:23])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C(N(CC)CC)C>[I-].[K+].CN(C)C=O>[F:12][C:9]1[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][CH2:2][N:18]2[CH2:19][CH2:20][C:15]([NH:21][C:22](=[O:24])[CH3:23])([CH3:14])[CH2:16][CH2:17]2)=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 743911-(3-Chloropropoxy)-4-fluorobenzeneHCID 21472474155928-36-2

Product 1

HCID 21472471N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]acetamideYield 39.6%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 35.84 g of 1-(3-chloropropoxy)-4-fluorobenzene, 33 g of N-(4-methyl-4-piperidinyl)acetamide monohydrochloride, 54 ml of N,N-diethylethanamine, 0.1 g of potassium iodide and 1000 ml of N,N-dimethylformamide was stirred and heated for 1.5 hours at 70° C. The reaction mixture was cooled and the solvent was evaporated. The residue was taken up in a sodium carbonate solution in water and the product was extracted with dichloromethane. The extract was washed successively twice with water, twice with a sodium carbonate solution in water and again with water, dried, filtered and evaporated. The residue was purified by column chromatography (CHCl3 :CH3OH 95:5 by volume). The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried in vacuo at 50° C., yielding 20.93 g of N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]acetamide; mp. 103.4° C. (interm. 2).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe solvent was evaporated
  3. extractionthe product was extracted with dichloromethane
  4. washThe extract was washed successively twice with water, twice with a sodium carbonate solution in water and again with water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography (CHCl3 :CH3OH 95:5 by volume)
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from 2,2'-oxybispropane
  12. filtrationThe product was filtered off
  13. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-b1b0575c2d4d49b7857417c277b69364
Source dataset
uspto-grants-1997_11
Patent number
US05691358

Reaction notes

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