Hydrochloric Acid → HCID 68502461, compound

HRID 1963462Notes

Reaction equation

HRID 1963462 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]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[C:20]([CH3:28])[CH:19]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:32]O.Cl>CO.O.C(OCC)C>[CH3:28][C:20]1[CH:19]=[C:18]([C@H:10]2[CH2:9][C@@H:8]([C:6]3[O:7][NH:32][C:4](=[O:3])[CH:5]=3)[CH2:13][CH2:12][N:11]2[C:14]([O:16][CH3:17])=[O:15])[CH:23]=[CH:22][C:21]=1[C:24]([F:27])([F:26])[F:25]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730425HCID 131730425, compound

Product 1

HCID 68502461HCID 68502461, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-40 °C

Procedure

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3-methyl-4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (1.4 g, 3.37 mmol) was dissolved in MeOH (20 mL) and cooled to −40° C. NaOH (0.135 g, 3.37 mmol) dissolved in water (2 mL) was added during 10 min and the resulting colourless solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.223 g, 3.37 mmol) was added dropwise. The resulting solution was stirred at −40° C. for 30 min. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M HCl and the mixture continued to stir at 80° C. for 20 min. The mixture was dissolved between diethyl ether and water. The phases were separated and the organic phase was dried over Na2SO4, filtered through celite and the solvent removed. Purified by preparative HPLC. Gradient eluation using acetonitrile-acidic buffer, started 40-60 and ended 55-45. Cis-methyl 2-(3-methyl-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.37 g, 29%) was isolated. 1H NMR (600 MHz, cdcl3) δ 1.80-1.87 (m, 1H), 2.07-2.28 (m, 2H), 2.31-2.38 (m, 1H), 2.41 (s, 3H), 3.03-3.10 (m, 1H), 3.35-3.43 (m, 1H), 3.66 (s, 3H), 4.13-4.19 (m, 1H), 5.09 (t, 1H), 5.52 (s, 1H), 7.02-7.06 (m, 2H), 7.49 (d, 1H). MS m/z 385 (M+H)+

Workup

  1. additionwas added during 10 min
  2. stirringThe resulting solution was stirred at −40° C. for 30 min
  3. stirringto stir at 80° C. for 20 min
  4. customThe phases were separated
  5. dry with materialthe organic phase was dried over Na2SO4
  6. filtrationfiltered through celite
  7. customthe solvent removed
  8. customPurified by preparative HPLC

Sources & evidence

ORD record
ord-f857a8ddb4fc4254b2e1e7b836b8339f
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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