Sodium Hydroxide → Methyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate

HRID 576036Notes

Reaction equation

HRID 576036 reaction equation
[OH-:1].[Na+].S(O)(O)(=O)=O.[NH2:8]O.[Cl:10][C:11]1[CH:12]=[C:13]([C:18]([C:36]([F:39])([F:38])[F:37])=[CH:19][C:20]([C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]([C:32]([O:34][CH3:35])=[O:33])=[CH:24][CH:23]=2)=O)[CH:14]=[C:15]([Cl:17])[CH:16]=1>O.O1CCCC1.CO>[Cl:10][C:11]1[CH:12]=[C:13]([C:18]2([C:36]([F:39])([F:38])[F:37])[O:1][N:8]=[C:20]([C:22]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:25]([C:32]([O:34][CH3:35])=[O:33])=[CH:24][CH:23]=3)[CH2:19]2)[CH:14]=[C:15]([Cl:17])[CH:16]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 159255Hydroxylamine, sulfate (1:1)HCID 66865184Methyl 4-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-1-naphthalenecarboxylate

Product 1

HCID 58338637Methyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylateYield 87%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydroxide (50%, 3.50 g, 43.7 mmol) was added to a solution of hydroxylamine sulfate (1.8 g, 11.0 mmol) in water (22 mL). When the mixture had cooled to room temperature a portion of the mixture (˜50%) was added dropwise over 4 minutes to methyl 4-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-1-naphthalene-carboxylate (i.e. the product of Step A) (5.00 g, 11.0 mmol) in tetrahydrofuran (55 mL) at room temperature. After 30 minutes a further portion (˜10%) of the aqueous mixture was added. The mixture was stirred for a further 15 minutes. The mixture was partitioned between hydrochloric acid (1 N, 50 mL) and tert-butyl methyl ether (50 mL). The organic phase was evaporated, and the solid obtained was stirred in hot methanol. The mixture was cooled and filtered to give the product as a white solid (4.50 g, 87%) melting at 137.3-138° C. (after recrystallization from methanol). The following spectra were of the product recrystallized from methanol.

Workup

  1. customThe mixture was partitioned between hydrochloric acid (1 N, 50 mL) and tert-butyl methyl ether (50 mL)
  2. customThe organic phase was evaporated
  3. customthe solid obtained
  4. temperatureThe mixture was cooled
  5. filtrationfiltered

Sources & evidence

ORD record
ord-5b532408bb55480db4a7262a42809705
Source dataset
uspto-grants-2015_05
Patent number
US09035101B2

Reaction notes

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