Hydrochloric Acid → HCID 56944308, compound

HRID 1950717Notes

Reaction equation

HRID 1950717 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:35]([F:38])([F:37])[F:36])[O:14][N:13]=[C:12]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]([C:25]([NH:27][CH2:28][C:29](=O)[C:30]([F:33])([F:32])[F:31])=[O:26])=[CH:17][CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8].[NH2:39][OH:40].Cl.CC([O-])=O.[K+]>CCO.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:35]([F:36])([F:37])[F:38])[O:14][N:13]=[C:12]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]([C:25]([NH:27][CH2:28]/[C:29](=[N:39]\[OH:40])/[C:30]([F:33])([F:31])[F:32])=[O:26])=[CH:17][CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 517044Potassium AcetateHCID 86663502HCID 86663502, compound

Product 1

HCID 56944308HCID 56944308, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
130 °C

Procedure

To a solution of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(3,3,3-trifluoro-2-oxopropyl)-1-naphthamide (Preparation 11, 100 mg, 0.2 mmol) in EtOH (5 mL) was added hydroxylamine.HCl (30 mg, 0.4 mmol), water (1 mL), and KOAc (40 mg, 0.4 mmol). Reaction was heated to 130° C. for 40 minutes in a microwave. Water was added to the crude reaction and extracted with EtOAc (2×75 mL). The combined organics were dried (Na2SO4) and concentrated under vacuum. The crude material was chromatographed (24 g Redi-Sep column) eluting from 100% EtOAc to 50:50 EtOAc:heptane to afford (E)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(3,3,3-trifluoro-2-(hydroxyimino)-propyl)-1-naphthamide (52 mg, 51%) as a solid. 1HNMR (CDCl3) δ ppm: 9.06 (1H), 8.81 (1H), 8.26 (1H), 7.71-7.57 (4H), 7.51 (1H), 6.48 (1H), 4.64 (2H) 4.28 (1H), 3.89 (1H); m/z (Cl) 596 [M+H]+.

Workup

  1. customReaction
  2. customreaction
  3. extractionextracted with EtOAc (2×75 mL)
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. concentrationconcentrated under vacuum
  6. customThe crude material was chromatographed (24 g Redi-Sep column)
  7. washeluting from 100% EtOAc to 50:50 EtOAc

Sources & evidence

ORD record
ord-616b4524c5024fba98a0c49b58fa72be
Source dataset
uspto-grants-2013_03
Patent number
US08404649B2

Reaction notes

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