Hydrochloric Acid → HCID 131730412, compound

HRID 1963437Notes

Reaction equation

HRID 1963437 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([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:5]=[C:6]([Cl:8])[CH:7]=1.[OH-].[Na+].[NH2:29]O.Cl>CO.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:14][C@H:13]([C:15]3[O:22][NH:29][C:17](=[O:18])[CH:16]=3)[CH2:12][CH2:11][N:10]2[C:23]([O:25][CH3:26])=[O:24])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730410HCID 131730410, compound

Product 1

HCID 131730412HCID 131730412, compoundYield 54.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-40 °C

Procedure

Trans-methyl 2-(3,5-dichlorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (0.6 g, 1.49 mmol) (from example 55, step 1) was dissolved in MeOH (6.11 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.393 mL, 1.49 mmol) in water (0.611 mL) was added and the mixture stirred at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.091 mL, 1.49 mmol) was added and stirring continued at −40° C. for 3.5 h. The reaction mixture was then transferred to a preheated 80° C. solution of 6 M hydrogen chloride (7.71 mL, 46.24 mmol) and heating was continued for 20 min. The solvent was then evaporated. DCM and water were added, shaken and the phases separated. The organic phase was dried with a phase separator and evaporated to yield crude trans-methyl 2-(3,5-dichlorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (300 mg, 54%). MS m/z 371 (M+H)+

Workup

  1. stirringstirring
  2. waitcontinued at −40° C. for 3.5 h
  3. customwas then transferred to a preheated 80° C.
  4. temperatureheating
  5. waitwas continued for 20 min
  6. customThe solvent was then evaporated
  7. additionDCM and water were added
  8. stirringshaken
  9. customthe phases separated
  10. customThe organic phase was dried with a phase separator
  11. customevaporated

Sources & evidence

ORD record
ord-8c3d3e06ea194fe48f7ac834680bd90e
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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