Hydrochloric Acid → HCID 131730415, compound

HRID 1963442Notes

Reaction equation

HRID 1963442 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6]([C@@H:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH3:17])=[O:15])[C@@H:10]([C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][C:19]=2[F:29])[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:33]O.Cl>CO.O.C(Cl)Cl>[F:29][C:19]1[CH:20]=[C:21]([O:24][C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:23][C:18]=1[C@H:10]1[CH2:9][C@H:8]([C:6]2[O:7][NH:33][C:4](=[O:3])[CH:5]=2)[CH2:13][CH2:12][N:11]1[C:14]([O:16][CH3:17])=[O:15]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730414trans-Methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2-fluoro-4-(trifluoromethoxy)phenyl)piperidine-1-carboxylate

Product 1

HCID 131730415HCID 131730415, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2-fluoro-4-(trifluoromethoxy)phenyl)-piperidine-1-carboxylate (420 mg, 0.96 mmol) (from example 58, step 1) was dissolved in MeOH (4 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (40.5 mg, 1.01 mmol) dissolved in water (0.400 mL) was added and the mixture was stirred at −40° C. for 15 min. Hydroxylamine (50% by weight in water, 62 μL, 1.01 mmol) was added. The resulting solution was stirred at −40° C. for 1 h. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (4.98 mL, 29.91 mmol) and the mixture was stirred at 80° C. for 15 min. Water and DCM were added and the phases separated. The aqueous phase was extracted with DCM and the combined organic layers were filtered through a phase separator and evaporated. Crude trans-methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (365 mg, 94%) was yielded as a colorless oil. MS m/z 405 (M+H)+

Workup

  1. additionwas added
  2. stirringThe resulting solution was stirred at −40° C. for 1 h
  3. stirringthe mixture was stirred at 80° C. for 15 min
  4. customthe phases separated
  5. extractionThe aqueous phase was extracted with DCM
  6. filtrationthe combined organic layers were filtered through a phase separator
  7. customevaporated

Sources & evidence

ORD record
ord-a9ce1ed36dfc4e01a79846caedd8e05c
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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