Hydrochloric Acid → HCID 131730383, compound

HRID 1963365Notes

Reaction equation

HRID 1963365 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]([F:24])=[CH:20][CH:19]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:28]O.Cl>CO.O>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C@H:10]2[CH2:9][C@H:8]([C:6]3[O:7][NH:28][C:4](=[O:3])[CH:5]=3)[CH2:13][CH2:12][N:11]2[C:14]([O:16][CH3:17])=[O:15])=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730381HCID 131730381, compound

Product 1

HCID 131730383HCID 131730383, compoundYield 95.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-40 °C

Procedure

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-fluorophenyl)piperidine-1-carboxylate (1.26 g, 3.59 mmol) (from example 25, step 1) was dissolved in MeOH (50 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.143 g, 3.59 mmol) dissolved in water (5.00 mL) was added during 5 min and the colourless solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.220 mL, 3.59 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 3 h 20 min. The mixture was transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (17.93 mL, 107.58 mmol) and the mixture continued to stir at 80° C. for 20 min. The solvent was evaporated and DCM/water added. The phases were separated and the organic phase passed through a phase separator and evaporated to yield trans-methyl 2-(4-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.1 g, 95%) as a brown solid, 1.1 g. MS m/z 321 (M+H)+.

Workup

  1. additionwas added during 5 min
  2. stirringThe resulting solution was stirred at −40° C. for 3 h 20 min
  3. stirringto stir at 80° C. for 20 min
  4. customThe solvent was evaporated
  5. additionDCM/water added
  6. customThe phases were separated
  7. customevaporated

Sources & evidence

ORD record
ord-eab755d29de74ab49bbf2ec1c882bee0
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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