Hydrochloric Acid → HCID 66731863, compound

HRID 1963590Notes

Reaction equation

HRID 1963590 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH3:17])=[O:15])[CH:10]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:32]O.Cl>CO.O.C(OCC)(=O)C>[CH3:28][S:25]([C:22]1[CH:23]=[CH:24][C:19]([CH2:18][CH:10]2[CH2:9][CH:8]([C:6]3[O:7][NH:32][C:4](=[O:3])[CH:5]=3)[CH2:13][CH2:12][N:11]2[C:14]([O:16][CH3:17])=[O:15])=[CH:20][CH:21]=1)(=[O:27])=[O:26]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 66732596HCID 66732596, compound

Product 1

HCID 66731863HCID 66731863, compoundYield 28.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

Methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(methylsulfonyl)benzyl)piperidine-1-carboxylate (3.99 g, 9.38 mmol) was dissolved in MeOH (70 mL) and cooled to −30° C. NaOH (0.375 g, 9.38 mmol) dissolved in water (7 mL) was added during 10 min and the resulting colourless solution continued to stir at −30° C. for 20 min. Hydroxylamine (50% by weight in water, 0.575 mL, 9.38 mmol) was added dropwise. The resulting solution was stirred at −30° C. for 30 min. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M HCl (30 mL, 180 mmol) and the mixture continued to stir at 80° C. for 20 min. The mixture was dissolved between ethyl acetate and water. The aqueous layer was extracted three more times with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered through celite and the solvent was evaporated. The residue was purified using reversed phase chromatography, gradient acid buffer and acetonitril, started 35% and ended 40%. Methyl 2-(4-(methylsulfonyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.05 g, 28.4%) was isolated.

Workup

  1. additionwas added during 10 min
  2. stirringThe resulting solution was stirred at −30° C. for 30 min
  3. stirringto stir at 80° C. for 20 min
  4. extractionThe aqueous layer was extracted three more times with ethyl acetate
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered through celite
  7. customthe solvent was evaporated
  8. customThe residue was purified

Sources & evidence

ORD record
ord-b0ce4b95b6a34f5a945f274f5eb66399
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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