Hydrochloric Acid → HCID 131730426, compound

HRID 1963466Notes

Reaction equation

HRID 1963466 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 131730424HCID 131730424, compound

Product 1

HCID 131730426HCID 131730426, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-40 °C

Procedure

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3-methyl-4-(trifluoromethyl)phenyl)-piperidine-1-carboxylate (0.69 g, 1.66 mmol) (from example 67, step 1) was dissolved in MeOH (8 mL) and cooled to −40° C. under nitrogen. NaOH (0.066 g, 1.66 mmol) dissolved in water (0.7 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, 0.110 g, 1.66 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 evaporated to yield crude trans-methyl 2-(3-methyl-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.54 g, 85%). 1H NMR (600 MHz, cdcl3) δ 1.60-1.72 (m, 1H), 1.89-1.97 (m, 1H), 1.99-2.07 (m, 1H), 2.48 (s, 3H), 2.58-2.71 (m, 1H), 2.80 (s, 1H), 2.93 (t, 1H), 3.73 (s, 3H), 4.23 (s, 1H), 5.49-5.73 (m, 2H), 7.06-7.16 (m, 2H), 7.60 (d, 1H).

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. customevaporated

Sources & evidence

ORD record
ord-ace4cd0ca68947e49ad9ebd4bbef0eb2
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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