Hydrochloric Acid → HCID 66739246, compound

HRID 1963405Notes

Reaction equation

HRID 1963405 reaction equation
[C:1]([C:5]1[S:9][C:8]([C@H:10]2[CH2:15][C@@H:14]([C:16](=[O:23])[CH2:17][C:18](OCC)=[O:19])[CH2:13][CH2:12][N:11]2[C:24]([O:26][CH3:27])=[O:25])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[NH2:30]O.Cl>CO.O>[C:1]([C:5]1[S:9][C:8]([C@H:10]2[CH2:15][C@@H:14]([C:16]3[O:23][NH:30][C:18](=[O:19])[CH:17]=3)[CH2:13][CH2:12][N:11]2[C:24]([O:26][CH3:27])=[O:25])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730401HCID 131730401, compound

Product 1

HCID 66739246HCID 66739246, compoundYield 49.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-40 °C

Procedure

Cis-methyl 2-(5-tert-butylthiophen-2-yl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (963 mg, 2.43 mmol) was dissolved in methanol (15 mL) and cooled to −40° C. NaOH (0.641 mL, 2.43 mmol) dissolved in water (1 mL) was added and stirred for 20 min. Hydroxylamine (50% by weight in water, 0.149 mL, 2.43 mmol) was added and the reaction stirred at −40° C. for 3 h. The reaction mixture was then added to a prewarmed 80° C. solution of 6 M HCl (12.58 mL, 75.48 mmol) and stirred for 20 min. The solvent was evaporated in vacuo. DCM (150 mL) and water (150 mL) were added, shaken and the phases separated. The aqueous phase was extracted with DCM (150 mL). The combined organic phase were dried with a phase separator and evaporated in vacuo. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 35-75% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer over 25 minutes with a flow of 100 mL/min. Cis-methyl 2-(5-tert-butylthiophen-2-yl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (436 mg, 49.1%) was isolated as a white solid. MS m/z 363 (M−H)−

Workup

  1. additionwas added
  2. stirringthe reaction stirred at −40° C. for 3 h
  3. stirringstirred for 20 min
  4. customThe solvent was evaporated in vacuo
  5. additionDCM (150 mL) and water (150 mL) were added
  6. stirringshaken
  7. customthe phases separated
  8. extractionThe aqueous phase was extracted with DCM (150 mL)
  9. customThe combined organic phase were dried with a phase separator
  10. customevaporated in vacuo
  11. customThe compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm)
  12. custombuffer over 25 minutes

Sources & evidence

ORD record
ord-71a93207653e4e6593346e43da62b568
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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