Hydrochloric Acid → HCID 66740525, compound

HRID 1963400Notes

Reaction equation

HRID 1963400 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:19]=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:31]O.Cl>CO>[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]([C:18]3[CH:19]=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=3)[CH2:9]2)[O:7][NH:31]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730399HCID 131730399, compound

Product 1

HCID 66740525HCID 66740525, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-45 °C

Procedure

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(6-(trifluoromethyl)pyridin-3-yl)piperidine-1-carboxylate (1.085 g, 2.70 mmol) was dissolved in MeOH (12 mL) and cooled to −45° C. under nitrogen. Sodium hydroxide (0.793 mL, 2.70 mmol) was added during 10 min and the yellow solution continued to stir at −45° C. for 20 min. Hydroxylamine (50% by weight in water, 0.165 mL, 2.70 mmol) was added during 8 min. The resulting solution was stirred at −45° C. for 3 h. The mixture was then rapidly poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (13.89 mL, 83.32 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 a white solid. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 10-60% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. Cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)piperidine-1-carboxylate (160 mg, 16%) was isolated. MS m/z 372 (M+H)+

Workup

  1. stirringThe resulting solution was stirred at −45° C. for 3 h
  2. stirringto stir at 80° C. for 20 min
  3. customThe solvent was evaporated
  4. additionDCM/water added
  5. customThe phases were separated
  6. customevaporated
  7. customto yield a white solid
  8. customThe compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm)
  9. custombuffer over 30 minutes

Sources & evidence

ORD record
ord-c6222f4e353a4faea435ce329cd2e1c1
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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