Hydrochloric Acid → HCID 68503711, compound

HRID 1963409Notes

Reaction equation

HRID 1963409 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][C@@H:13]([C:15](=[O:22])[CH2:16][C:17](OCC)=[O:18])[CH2:12][CH2:11][N:10]1[C:23]([O:25][CH3:26])=[O:24].[OH-].[Na+].[NH2:29]O.Cl>CO>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][C@@H:13]([C:15]2[O:22][NH:29][C:17](=[O:18])[CH:16]=2)[CH2:12][CH2:11][N:10]1[C:23]([O:25][CH3:26])=[O:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730402cis-Methyl 2-(2,4-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate

Product 1

HCID 68503711HCID 68503711, compoundYield 49.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-45 °C

Procedure

Cis-methyl 2-(2,4-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (870 mg, 2.36 mmol) was dissolved in MeOH (9 mL) and cooled to −45° C. under nitrogen. Sodium hydroxide (0.693 mL, 2.36 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, 0.144 mL, 2.36 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 (12.13 mL, 72.78 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 2-(2,4-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (397 mg, 49%) was isolated. MS m/z 339 (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-13b352bb2c21435bab9a7ccf43fc7c64
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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