Sodium Hydroxide → 3-(4-Chlorobenzo[b]thiophen-2-yl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole

HRID 240889Notes

Reaction equation

HRID 240889 reaction equation
[Cl:1][C:2]1[C:10]2[CH:9]=[C:8]([C:11](=O)[CH:12]=[C:13]([C:18]3[CH:23]=[C:22]([Cl:24])[CH:21]=[C:20]([Cl:25])[CH:19]=3)[C:14]([F:17])([F:16])[F:15])[S:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[OH-:27].[Na+].[NH2:29]O.Cl>CO.O>[Cl:1][C:2]1[C:10]2[CH:9]=[C:8]([C:11]3[CH2:12][C:13]([C:18]4[CH:23]=[C:22]([Cl:24])[CH:21]=[C:20]([Cl:25])[CH:19]=4)([C:14]([F:17])([F:16])[F:15])[O:27][N:29]=3)[S:7][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 866937471-(4-Chlorobenzo[b]thiophen-2-yl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-en-1-one

Product 1

HCID 714689443-(4-Chlorobenzo[b]thiophen-2-yl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazoleYield 28.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Stir a mixture of 1-(4-chlorobenzo[b]thiophen-2-yl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-en-1-one (1.05 g, crude, 2.43 mmol), NaOH (389 mg, 9.72 mmol) and NH2OH—HCl (335 mg, 4.8 mmol) in MeOH (8 mL) and water (8 mL) at ambient temperature for 4 hours. After removal of solvent under vacuum, dilute the residue with ice water (20 mL). Extract the aqueous mixture with EtOAc (15 mL×3). The combined organic layers are washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. Purify the residue by preparative HPLC to afford 3-(4-chlorobenzo[b]thiophen-2-yl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole as white solid (305 mg, 28.1%). MS (m/z): 450 (M+1). 1H NMR (400 MHz, CDCl3) δδ 7.74 (d, J=8.0, 1H), 7.64-7.60 (s, 1H), 7.57-7.53 (m, 2H), 7.47-7.43 (m, 1H), 7.40-7.32.

Workup

  1. customAfter removal of solvent under vacuum
  2. additiondilute the residue with ice water (20 mL)
  3. extractionExtract the aqueous mixture with EtOAc (15 mL×3)
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under vacuum
  7. customPurify the residue by preparative HPLC

Sources & evidence

ORD record
ord-3a05fb54f28c4196963f42ee45383ae9
Source dataset
uspto-grants-2014_02
Patent number
US08648081B2

Reaction notes

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