Sodium Hydroxide → 4-(4-Fluorophenyl)-1-methyl-4-piperidinamine

HRID 493441Notes

Reaction equation

HRID 493441 reaction equation
C1(P([N:15]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.Cl.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2(C(O)=O)[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)=[CH:22][CH:21]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.Cl>[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2([NH2:15])[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 199401P,P-Diphenylphosphinic azideHCID 67528606HCID 67528606, compound

Product 1

HCID 497607944-(4-Fluorophenyl)-1-methyl-4-piperidinamine

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

TEA (1.3 mL) and diphenylphosphorylazide (0.98 mL) were added to a suspension of 4-(4-fluorophenyl)-1-methyl-4-piperidinecarboxylic acid hydrochloride (500 mg) in dry toluene (40 mL) under nitrogen atmosphere. The reaction mixture was heated at 90° C. and stirred overnight. Then it was cooled to rt and washed with an aqueous std K2CO3 solution. The aqueous layer was separated and the organic phase was dried and concentrated under vacuum to give a white solid. This material was suspended in HCl 5M (10 mL) and the reaction mixture was heated to reflux and stirred overnight. Then it was cooled to 0° C. and treated with aqueous 4M NaOH solution until pH=9. The aqueous layer was extracted with AcOEt, the combined organic extracts were washed with water and brine, dried and concentrated under vacuum to a residue which was purified by silica cartridge (from DCM to DCM/MeOH/TEA 90:5:5) to give the title compound (70 mg) as a white foam.

Workup

  1. temperatureThen it was cooled to rt
  2. washwashed with an aqueous std K2CO3 solution
  3. customThe aqueous layer was separated
  4. customthe organic phase was dried
  5. concentrationconcentrated under vacuum
  6. customto give a white solid
  7. temperaturethe reaction mixture was heated
  8. temperatureto reflux
  9. stirringstirred overnight
  10. temperatureThen it was cooled to 0° C.
  11. extractionThe aqueous layer was extracted with AcOEt
  12. washthe combined organic extracts were washed with water and brine
  13. customdried
  14. concentrationconcentrated under vacuum to a residue which
  15. customwas purified by silica cartridge (from DCM to DCM/MeOH/TEA 90:5:5)

Sources & evidence

ORD record
ord-f91bf495fa3044ce93949c323e8c0016
Source dataset
uspto-grants-2009_05
Patent number
US07534893B2

Reaction notes

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