Hydrochloric Acid → HCID 131730400, compound
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]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -45 °C
Procedure
Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(6-(trifluoromethyl)pyridin-3-yl)piperidine-1-carboxylate (70 mg, 0.17 mmol) (from example 40, step 1) was dissolved in MeOH (1 mL) and cooled to −45° C. under nitrogen. Sodium hydroxide (0.051 mL, 0.17 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, 10.66 μL, 0.17 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 (0.896 mL, 5.38 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 crude trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)piperidine-1-carboxylate (60 mg, quant.) as a slightly yellow oil. MS m/z 372 (M+H)+
Workup
- stirringThe resulting solution was stirred at −45° C. for 3 h
- stirringto stir at 80° C. for 20 min
- customThe solvent was evaporated
- additionDCM/water added
- customThe phases were separated
- customevaporated
Sources & evidence
- ORD record
- ord-29dc34b46a62463b84a12c7f34fe6e3c
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415378B2
Reaction notes
Loading…