Hydrochloric Acid → HCID 131730418, 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:23]=[C:22]([F:24])[C:21]([F:25])=[C:20]([F:26])[CH:19]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:30]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:23]=[C:22]([F:24])[C:21]([F:25])=[C:20]([F:26])[CH:19]=3)[CH2:9]2)[O:7][NH:30]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -40 °C
Procedure
Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (59 mg, 0.15 mmol) (from example 60, step 1) was dissolved in MeOH (1 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.045 mL, 0.15 mmol) was added during 10 min and the yellow solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 9.33 μL, 0.15 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 3 h 15 min. The mixture was then rapidly poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (0.784 mL, 4.71 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, the organic phase passed through a phase separator and evaporated to yield crude trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (53 mg, quant.) as a slightly yellow oil. MS m/z 357 (M+H)+
Workup
- stirringThe resulting solution was stirred at −40° C. for 3 h 15 min
- 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-db46ec76a1504998bf1106b3224b3b36
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415378B2
Reaction notes
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