Hydrochloric Acid → HCID 68500325, compound

HRID 1963561Notes

Reaction equation

HRID 1963561 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+].Cl.[NH2:33]O.Cl>CO.CO.O.C(OCC)(=O)C.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:33]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 443297Hydroxyamine hydrochlorideHCID 131730466HCID 131730466, compound

Product 1

HCID 68500325HCID 68500325, compoundYield 55.6%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 22242641Methanol--water (1/1)Solvent2×

Procedure

A solution of trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(trifluoromethyl)benzyl)-piperidine-1-carboxylate (0.4 g, 0.96 mmol) in methanol (3 mL) was added dropwise to a solution of NaOH (0.042 g, 1.06 mmol) in methanol/water (3 mL/0.2 mL) at −30° C. After stirring for 10 min a solution of hydroxylamine hydrochloride (0.134 g, 1.93 mmol) and NaOH (0.077 g, 1.93 mmol) in methanol/water (5 mL/5 mL) was added at −30° C. Stirring was continued for 30 min at −30° C. The solution was added dropwise to 6 M HCl at 80° C. Stirred 30 min at 80° C. The reaction mixture was dissolved between water and ethyl acetate. The organic phase was isolated, dried with Na2SO4, filtered through celite and the solvent was evaporated. Acidic reversed phase chromatography, gradient 35% to 75% acetonitrile. Trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (205 mg, 55.4%) was isolated. 1H NMR (600 MHz, cdcl3) δ 1.63 (d, 2H), 1.98 (d, 2H), 2.81-3.14 (m, 4H), 3.55 (d, 3H), 4.21 (d, 1H), 4.63 (d, 1H), 5.63 (s, 1H), 7.22-7.37 (m, 2H), 7.54 (d, 2H). MS m/z 385 (M+H)+

Workup

  1. additionwas added at −30° C
  2. stirringStirred 30 min at 80° C
  3. customThe organic phase was isolated
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered through celite
  6. customthe solvent was evaporated

Sources & evidence

ORD record
ord-38d6a5b1176e4131b23c066504d93583
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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