Hydrochloric Acid → HCID 131730495, compound

HRID 1963637Notes

Reaction equation

HRID 1963637 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]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([F:29])[CH:20]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:33]O.Cl>CO.O>[F:29][C:21]1[CH:20]=[C:19]([CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=1)[CH2:18][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

7

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730493HCID 131730493, compound

Product 1

HCID 131730495HCID 131730495, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-40 °C

Procedure

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3-fluoro-5-(trifluoromethyl)benzyl)piperidine-1-carboxylate (0.75 g, 1.73 mmol) (from example 137, step 1) was dissolved in MeOH (15 mL) and cooled to −40° C. Sodium hydroxide (0.073 g, 1.82 mmol) dissolved in water (1 mL) was added over 1 min and the resulting solution was stirred at −40° C. for 20 min. Then hydroxylamine (50% by weight in water, 0.115 mL, 1.88 mmol) was added over 1 min and stirring continued at −40° C. for 2 h 20 min. The reaction mixture was then transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (30 mL, 180.00 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 MgSO4 and evaporated. Trans-methyl 2-(3-fluoro-5-(trifluoromethyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (658 mg, 95%) was isolated as an off-white solid. MS m/z 403 (M+H)+

Workup

  1. additionwas added over 1 min
  2. stirringstirring
  3. waitcontinued at −40° C. for 2 h 20 min
  4. stirringto be stirred at 80° C. for 1 h
  5. temperatureThen cooled to room temperature
  6. customMethanol was evaporated
  7. additionwater was added
  8. extractionExtracted three times with DCM
  9. dry with materialCombined organic layers dried over MgSO4
  10. customevaporated

Sources & evidence

ORD record
ord-954065c2ed094adf930b4f6f4cf0bb65
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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