Hydrochloric Acid → HCID 131730478, compound

HRID 1963587Notes

Reaction equation

HRID 1963587 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][CH:7]2[CH2:12][CH: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 66732495HCID 66732495, compound

Product 1

HCID 131730478HCID 131730478, compoundYield 38.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

A solution of methyl 2-(4-chlorobenzyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (780 mg, 2.04 mmol) (from example 115, step 2) in MeOH (5 mL) was added to a solution of sodium hydroxide (1.705 mL, 2.05 mmol) in MeOH/H2O (1.608 mL/0.097 mL) at −30° C. After 10 min a solution of hydroxylamine hydrochloride (284 mg, 4.09 mmol) and sodium hydroxide (163 mg, 4.09 mmol) in MeOH (5 mL) and H2O (5 mL) was added. Stirring was continued at −30° C. for 30 min. The reaction solution was poured into 6 M HCl (3.40 mL, 20.43 mmol) at 80° C. and heated at 80° C. for 30 min. Concentration of the organic solvent and extraction with diethyl ether (×3), drying over Na2SO4 and evaporation gave a yellow foam. Purification using prepLC (pH=3, large column 20-80% MeCN over 30 min) yielded trans-methyl 2-(4-chlorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (272.5 mg, 38%). 1H NMR (400 MHz, cdcl3) δ 1.44-2.18 (m, 4H), 2.70-3.01 (m, 2H), 3.02-3.14 (m, 2H), 3.42-3.76 (m, 3H), 4.04-4.37 (m, 1H), 4.39-4.79 (m, 1H), 5.64 (s, 1H), 7.05-7.31 (m, 4H). 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(pH=3, large column 20-80% MeCN over 30 min)

Sources & evidence

ORD record
ord-8b45bcba825846ccb3e964d630ebb2a1
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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