Hydrochloric Acid → HCID 17906301, compound

HRID 852092Notes

Reaction equation

HRID 852092 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:16]3[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:15]=3[O:14][N:13]=2)=[CH:8][CH:7]=1.[NH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].[K+].[K+].Cl>C(#N)C>[F:21][C:19]1[CH:18]=[CH:17][C:16]2[C:12]([C:9]3[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][CH2:2][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:7][CH:8]=3)=[N:13][O:14][C:15]=2[CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8082PiperidineHCID 11430Potassium CarbonateHCID 17906346HCID 17906346, compound

Product 1

HCID 17906301HCID 17906301, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Combine 3-[4-(3-bromo-propoxy)-phenyl]-6-fluoro-benzo[d]isoxazole (0.727 g, 2.08 mmol), piperidine (0.707 g, 8.30 mmol), potassium carbonate (0.575 g, 4.16 mmol) and acetonitrile (7.0 mL) and heat (75° C.) overnight. Cool (45° C.) reaction, filter through a Waters Sep-Pak 1 g Silica cartridge (ethyl acetate) and concentrate (in vacuo). Purify the crude product by column (silica) chromatography with a graded solvent mixture of 5% methanol in dichloromethane to 10% methanol in dichloromethane. Concentrate to give a colorless oil and dry under vacuum (0.6 mm Hg, room temperature) for 3 hours to obtain a waxy, off-white solid. Acidify the free base with ethereal HCl, recrystallize (ethanol:ethyl acetate) and dry (in vacuo, 0.6 mm Hg, 60° C.) for 3 hours to give the title compound as the salt (0.336 g, 41% Yield). Microanalysis (C, H, N) is consistent with the final, desired compound. mp=202-205° C.

Workup

  1. temperatureCool
  2. custom(45° C.) reaction
  3. filtrationfilter through a Waters Sep-Pak 1 g Silica cartridge (ethyl acetate)
  4. concentrationconcentrate (in vacuo)
  5. customPurify the crude product by column (silica) chromatography
  6. additionwith a graded solvent mixture of 5% methanol in dichloromethane to 10% methanol in dichloromethane
  7. concentrationConcentrate
  8. customto give a colorless oil
  9. customdry under vacuum (0.6 mm Hg, room temperature) for 3 hours
  10. customto obtain a waxy, off-white solid
  11. customrecrystallize (ethanol:ethyl acetate)
  12. customdry (in vacuo, 0.6 mm Hg, 60° C.) for 3 hours

Sources & evidence

ORD record
ord-54e617cd9c2941699d5b3089a0f46ee7
Source dataset
uspto-grants-2007_08
Patent number
US07253165B2

Reaction notes

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