Hydrochloric Acid → HCID 131730484, compound

HRID 1963609Notes

Reaction equation

HRID 1963609 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:3]=1[CH2:4][C@H:5]1[CH2:10][C@H:9]([C:11](=[O:18])[CH2:12][C:13](OCC)=[O:14])[CH2:8][CH2:7][N:6]1[C:19]([O:21][CH3:22])=[O:20].[OH-].[Na+].[NH2:30]O.Cl>CO.O>[F:1][C:2]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:3]=1[CH2:4][C@H:5]1[CH2:10][C@H:9]([C:11]2[O:18][NH:30][C:13](=[O:14])[CH:12]=2)[CH2:8][CH2:7][N:6]1[C:19]([O:21][CH3:22])=[O:20]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730482HCID 131730482, compound

Product 1

HCID 131730484HCID 131730484, compoundYield 98.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-40 °C

Procedure

Trans-methyl 2-(2,5-difluorobenzyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (0.611 g, 1.59 mmol) (from example 124, step 1) was dissolved in MeOH (5 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.064 g, 1.59 mmol) dissolved in water (0.500 mL) was added during 10 min and the colourless solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.098 mL, 1.59 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 3 h. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (8 mL, 48.00 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 2-(2,5-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.552 g, 98%) as a yellow semi-solid. MS m/z 353 (M+H)+

Workup

  1. additionwas added during 10 min
  2. stirringThe resulting solution was stirred at −40° C. for 3 h
  3. stirringto stir at 80° C. for 20 min
  4. customThe solvent was evaporated
  5. additionDCM/water added
  6. customThe phases were separated
  7. customevaporated

Sources & evidence

ORD record
ord-01bff378faba47699378fa55efc07652
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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