Hydrochloric Acid → HCID 131730394, compound

HRID 1963392Notes

Reaction equation

HRID 1963392 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C@H:11]2[CH2:16][C@H:15]([C:17](=[O:24])[CH2:18][C:19](OCC)=[O:20])[CH2:14][CH2:13][N:12]2[C:25]([O:27][CH3:28])=[O:26])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[NH2:31]O.Cl>CO.O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C@H:11]2[CH2:16][C@H:15]([C:17]3[O:24][NH:31][C:19](=[O:20])[CH:18]=3)[CH2:14][CH2:13][N:12]2[C:25]([O:27][CH3:28])=[O:26])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730393trans-Methyl 2-(4-tert-butylphenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate

Product 1

HCID 131730394HCID 131730394, compoundYield 90.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-40 °C

Procedure

Trans-methyl 2-(4-tert-butylphenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.09 g, 2.80 mmol) was dissolved in MeOH (10 mL) and cooled to −40° C. Sodium hydroxide (0.112 g, 2.80 mmol) dissolved in water (1.2 mL) was added over 1 min and the resulting solution was stirred at −40° C. for 20 min. Then, hydroxylamine (50% in water, 0.178 mL, 2.91 mmol) was added over 1 min and stirring continued at −40° C. for 3 h. The reaction mixture was then transferred into a prewarmed (80° C.) solution of 6M 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. Crude trans-methyl 2-(4-tert-butylphenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (910 mg, 90%) was isolated as off-white foam. 1H NMR (400 MHz, cdcl3) δ 1.32 (s, 9H), 1.46-2.23 (m, 3H), 2.46-3.05 (m, 3H), 3.74 (s, 3H), 3.98-4.43 (m, 1H), 5.48-5.72 (m, 2H), 7.10-7.22 (m, 2H), 7.35-7.45 (m, 2H). MS m/z 359 (M+H)+

Workup

  1. additionwas added over 1 min
  2. stirringstirring
  3. waitcontinued at −40° C. for 3 h
  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-0ed0a1dee47048179d15db4cadd8a9a3
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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