Hydrochloric Acid → HCID 68505771, compound

HRID 1963558Notes

Reaction equation

HRID 1963558 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]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:32]O.Cl>CO.O>[O:3]=[C:4]1[CH:5]=[C:6]([C@H:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][CH3:17])=[O:15])[C@@H:10]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[CH2:9]2)[O:7][NH:32]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730465HCID 131730465, compound

Product 1

HCID 68505771HCID 68505771, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-40 °C

Procedure

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (14.9 g, 35.87 mmol) was dissolved in MeOH (120 mL) and cooled to −40° C. Sodium hydroxide (1.495 g, 37.38 mmol) dissolved in water (14.4 mL) was added over 2 min and the resulting solution stirred at −40° C. for 20 min. Then hydroxylamine (50% by weight in water, 2.2 mL, 35.90 mmol) was added over 1 min and stirring continued between −40° C. and −45° C. for 80 min. The reaction mixture was then poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (400 mL, 2400.00 mmol) and the mixture was continued to be stirred at 80° C. for 1 h. Then cooled to room temperature. Methanol was evaporated, then water was added. Extracted three times with DCM. Combined organic layers dried over Na2SO4 and evaporated. Crude cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (12.88 g, 94%) was isolated. MS m/z 385 (M+H)+

Workup

  1. additionwas added over 2 min
  2. stirringstirring continued between −40° C. and −45° C. for 80 min
  3. stirringto be stirred at 80° C. for 1 h
  4. temperatureThen cooled to room temperature
  5. customMethanol was evaporated
  6. additionwater was added
  7. extractionExtracted three times with DCM
  8. dry with materialCombined organic layers dried over Na2SO4
  9. customevaporated

Sources & evidence

ORD record
ord-9e4f263f7ce84f16aa5266a7101fd774
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…