Hydrochloric Acid → HCID 18700426, compound

HRID 2288982Notes

Reaction equation

HRID 2288982 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:18][CH2:17][N:16](CC#N)[CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:22][O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:4][CH:3]=1.NN.[ClH:31].O>C(O)C>[ClH:31].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:22][O:23][CH2:24][C:25]([F:26])([F:27])[F:28])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 9321HydrazineHCID 53781901HCID 53781901, compound

Product 1

HCID 18700426HCID 18700426, compoundYield 90.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

A 5-l round bottom flask containing {4-[5-(4-fluorophenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperidin-1-yl} acetonitrile (313 g, 0.788 mole), 35% aqueous hydrazine (156 mL, 1.58 mole), 36% aqueous hydrochloric acid (130 mL, 1.58 mole), water (1 l) and ethanol (2 l) is warmed to 75° C. and stirred for 3.5 hours. The reaction mixture is cooled to room temperature, the solvent volume is reduced to 1.5 l by distillation and 3 N aqueous hydrochloric acid (1.5 l) is added. The aqueous solution is washed with dichloromethane (2×3 l). The combined organic extracts are dried over sodium sulfate (1 Kg), filtered and concentrated to effect crystallization (1.5 l). To complete the crystallization, methyl t-butylether (4 l) is added and the resulting slurry is cooled to 0° C. The solids are collected by filtration, washed with methyl t-butylether (750 mL) and dried to constant weight to give {4-[5-(4-fluorophenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperidine hydrochloride (280 g, 0.710 mole). 1H NMR (400 MHz, d6 DMSO) d 1.96 (m, 2H), 2.20 (m, 2H), 3.02 (q, 2H), 3.30 (m, 3H), 4.18 (q, 2H), 4.66 (s, 2H), 7.37 (t, 2H), 7.68 (q, 2H), 9.0 (bs, 1H), 9.20 (bs, 1H).

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. distillationthe solvent volume is reduced to 1.5 l by distillation and 3 N aqueous hydrochloric acid (1.5 l)
  3. additionis added
  4. washThe aqueous solution is washed with dichloromethane (2×3 l)
  5. dry with materialThe combined organic extracts are dried over sodium sulfate (1 Kg)
  6. filtrationfiltered
  7. concentrationconcentrated to effect crystallization (1.5 l)
  8. customthe crystallization, methyl t-butylether (4 l)
  9. additionis added
  10. temperaturethe resulting slurry is cooled to 0° C
  11. filtrationThe solids are collected by filtration
  12. washwashed with methyl t-butylether (750 mL)
  13. customdried to constant weight

Sources & evidence

ORD record
ord-06bc48e735e642bab4f0bcc9ec74e489
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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