Triethylamine → HCID 19982153, compound

HRID 1460504Notes

Reaction equation

HRID 1460504 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[O:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.[F:24][C:25]1[CH:26]=[CH:27][C:28]2[S:33][CH2:32][CH:31]([CH2:34]I)[CH2:30][C:29]=2[CH:36]=1>CN(C)C=O>[F:16][C:13]1[CH:12]=[CH:11][C:10]([C:8]([CH:5]2[CH2:6][CH2:7][N:2]([CH2:34][CH:31]3[CH2:30][C:29]4[CH:36]=[C:25]([F:24])[CH:26]=[CH:27][C:28]=4[S:33][CH2:32]3)[CH2:3][CH2:4]2)=[O:9])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 19982154HCID 19982154, compound

Product 1

HCID 19982153HCID 19982153, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
23 °C

Procedure

To a suspension of 2.178 kg (10.5 mol) p-fluorophenyl 4-piperidinyl ketone hydrochloride (R. L. Duncan et al., J. Med. Chem. 13, 1 (1970)), 1.008 kg (9.96 mol) triethylamine and 25 1 dimethylformamide is added a solution of 3.053 kg (9.9 mol) (6-fluoro-3,4-dihydro-2H-1-benzothiopyran-3-yl)methyl iodide in 9 1 dimethylformamide with stirring at 23° C. over 45 min. The suspension is stirred for 3 days at ambient temperature. The reaction is filtered and the filtrate concentrated at 80° C./4 mbar. The resulting oil is poured into a mixture of 20 1 water and 24 1 ethyl acetate, cooled to 5° C. and basified to pH 10 with concentrated ammonium hydroxide. The organic layer is separated, the aqueous solution extracted further with ethyl acetate, and the combined organic solutions washed with water and brine, dried over sodium sulfate and activated carbon, filtered, and concentrated at 50° C./ 4 mbar. The residue is triturated with heptane, filtered, washed twice with heptane, dried in vacuo and dissolved in dichloromethane. The solution is filtered from the insolubles, stirred with 1.27 kg Kieselgel 60 for 30 min., then filtered and evaporated at 45° C./4 mbar to give the title compound as a solid, m.p. 121°-124° C.

Workup

  1. stirringThe suspension is stirred for 3 days at ambient temperature
  2. filtrationThe reaction is filtered
  3. concentrationthe filtrate concentrated at 80° C./4 mbar
  4. additionThe resulting oil is poured into a mixture of 20 1 water and 24 1 ethyl acetate
  5. temperaturecooled to 5° C. and basified to pH 10 with concentrated ammonium hydroxide
  6. customThe organic layer is separated
  7. extractionthe aqueous solution extracted further with ethyl acetate
  8. washthe combined organic solutions washed with water and brine
  9. dry with materialdried over sodium sulfate and activated carbon
  10. filtrationfiltered
  11. concentrationconcentrated at 50° C./ 4 mbar
  12. customThe residue is triturated with heptane
  13. filtrationfiltered
  14. washwashed twice with heptane
  15. customdried in vacuo
  16. dissolutiondissolved in dichloromethane
  17. filtrationThe solution is filtered from the insolubles
  18. stirringstirred with 1.27 kg Kieselgel 60 for 30 min.
  19. filtrationfiltered
  20. customevaporated at 45° C./4 mbar

Sources & evidence

ORD record
ord-9238cd07492843d18fe776ca6ecc2ae1
Source dataset
uspto-grants-1991_12
Patent number
US05071858

Reaction notes

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