Hydrochloric Acid → HCID 68501730, compound

HRID 1963585Notes

Reaction equation

HRID 1963585 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C@H:7]2[CH2:12][C@@H:11]([C:13](=[O:20])[CH2:14][C:15](OCC)=[O:16])[CH2:10][CH2:9][N:8]2[C:21]([O:23][CH3:24])=[O:22])=[CH:4][CH:3]=1.[OH-].[Na+].Cl.[NH2:30]O.Cl>CO.CO.O.O>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C@H:7]2[CH2:12][C@@H:11]([C:13]3[O:20][NH:30][C:15](=[O:16])[CH:14]=3)[CH2:10][CH2:9][N:8]2[C:21]([O:23][CH3:24])=[O:22])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 443297Hydroxyamine hydrochlorideHCID 131730477HCID 131730477, compound

Product 1

HCID 68501730HCID 68501730, compoundYield 41.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

A solution of cis-methyl 2-(4-chlorobenzyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.45 g, 3.80 mmol) in MeOH (10 mL) was added to a solution of sodium hydroxide (3.16 mL, 3.80 mmol) in MeOH/H2O (2.981 mL/0.179 mL) at −30° C. After 10 min a solution of hydroxylamine hydrochloride (0.528 g, 7.59 mmol) and sodium hydroxide (0.304 g, 7.59 mmol) in MeOH (10 mL) and H2O (10 mL) was added. Stirring was continued at −30° C. for 30 min. The reaction solution was poured into 6 M HCl (6.33 mL, 37.97 mmol) at 80° C. and heated at 80° C. for 1 hour. Concentration of the organic solvent and extraction with diethyl ether (×3), drying over Na2SO4 and evaporation gave a yellow foam. Purification using prepLC (2 injections, pH=3, large column 20-80% MeCN over 30 min) yielded cis-methyl 2-(4-chlorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (557 mg, 41%). 1H NMR (400 MHz, cdcl3) δ 1.83-2.00 (m, 3H), 2.02-2.12 (m, 1H), 2.59 (dd, 1H), 2.77 (dd, 1H), 2.97-3.02 (m, 1H), 3.08-3.20 (m, 1H), 3.62 (s, 3H), 4.00 (dd, 1H), 4.21-4.29 (m, 1H), 5.73 (s, 1H), 7.04 (d, 2H), 7.21-7.25 (m, 2H). MS m/z 351, 353 (M+H)+

Workup

  1. extractionConcentration of the organic solvent and extraction with diethyl ether (×3)
  2. dry with materialdrying over Na2SO4 and evaporation
  3. customgave a yellow foam
  4. customPurification
  5. custom(2 injections, pH=3, large column 20-80% MeCN over 30 min)

Sources & evidence

ORD record
ord-cfeeddcc2916424c9916cb0af5c09984
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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