Hydrochloric Acid → HCID 131730423, compound

HRID 1963459Notes

Reaction equation

HRID 1963459 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C@H:9]2[CH2:14][C@H:13]([C:15](=[O:22])[CH2:16][C:17](OCC)=[O:18])[CH2:12][CH2:11][N:10]2[C:23]([O:25][CH3:26])=[O:24])=[CH:4][C:3]=1[F:27].[OH-].[Na+].[NH2:30]O.Cl>CO.O.C(Cl)Cl>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C@H:9]2[CH2:14][C@H:13]([C:15]3[O:22][NH:30][C:17](=[O:18])[CH:16]=3)[CH2:12][CH2:11][N:10]2[C:23]([O:25][CH3:26])=[O:24])=[CH:4][C:3]=1[F:27]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730422HCID 131730422, compound

Product 1

HCID 131730423HCID 131730423, compoundYield 96.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

Trans-methyl 2-(4-chloro-3,5-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (178 mg, 0.44 mmol) (from example 65, step 1) was dissolved in MeOH (2 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (18.51 mg, 0.46 mmol) dissolved in water (0.200 mL) was added and the mixture was stirred at −40° C. for 15 min. Hydroxylamine (50% by weight in water, 0.028 mL, 0.46 mmol) was added. The resulting solution was stirred at −40° C. for 1 h. The mixture was transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (2.278 mL, 13.67 mmol) and the mixture was stirred at 80° C. for 20 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-(4-chloro-3,5-difluorophenyl)-4-(3-oxo-2,3-dihydro-isoxazol-5-yl)piperidine-1-carboxylate (158 mg, 96%) was isolated as a light yellow oil. MS m/z 273 (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 20 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-64e32a3e495542989c9b1d6b4e7a8c6e
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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