Hydroxylamine → tert-butyl 2-methyl-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzoate

HRID 1770641Notes

Reaction equation

HRID 1770641 reaction equation
[CH3:1][C:2]1[CH:14]=[C:13]([C:15](=O)/[CH:16]=[C:17](/[C:22]2[CH:27]=[C:26]([Cl:28])[C:25]([Cl:29])=[C:24]([Cl:30])[CH:23]=2)\[C:18]([F:21])([F:20])[F:19])[CH:12]=[CH:11][C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[NH2:32][OH:33].O.[OH-].[Cs+]>C(Cl)(Cl)Cl.O.ClCCl>[CH3:1][C:2]1[CH:14]=[C:13]([C:15]2[CH2:16][C@:17]([C:22]3[CH:27]=[C:26]([Cl:28])[C:25]([Cl:29])=[C:24]([Cl:30])[CH:23]=3)([C:18]([F:21])([F:20])[F:19])[O:33][N:32]=2)[CH:12]=[CH:11][C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5]

Participants

7

Reactant 3

HCID 787HydroxylamineHCID 23679066Caesium hydroxide--water (1/1/1)HCID 86727017tert-butyl 2-methyl-4-[(Z)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-2-enoyl]benzoate

Product 1

HCID 86727016tert-butyl 2-methyl-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzoateYield 111.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-30 °C

Procedure

A 1500 mL reaction-vessel was charged at RT with 1-Anthracen-9-ylmethyl quininium chloride 13.77 mmol, 7.59 g) and tert-butyl 2-methyl-4-[(Z)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-2-enoyl]benzoate (68.87 mmol, 34 g) and dissolved in chloroform (700 mL). The mixture cooled down to −30° C. Then, a solution of hydroxylamine (50 mass % in H2O, 9.1 g) in water (50.9 mL) and cesium hydroxide hydrate (185.9 mmol, 32.88 g) in water (60 mL) were added simultaneously dropwise to the reaction mixture over 30 min. After the addition the reaction was kept 16 h at −30° C. after which time the conversion was complete. The reaction was brought to room temperature diluted with dichloromethane and washed three times with water. The organic phase was dried over MgSO4 and evaporated to yield crude title product. The product was purified over a silica gel column (eluent: EtOAc/Heptane) to obtain 39.0 g of the title product. LCMS (Method GR): RT 1.44 min, no ionisation: 1H NMR (400 MHz, CDCl3) 16.0 (s, 9H), 2.60 (s, 3H), 3.70 (d, 1H), 4.10-4.20 (m, 2H), 7.25-7.90 (m, 5H), 19F-NMR (CDCl3, 376 MHz): −79.40.

Workup

  1. additionAfter the addition the reaction
  2. customwas brought to room temperature
  3. washwashed three times with water
  4. dry with materialThe organic phase was dried over MgSO4
  5. customevaporated
  6. customto yield crude title product
  7. customThe product was purified over a silica gel column (eluent: EtOAc/Heptane)

Sources & evidence

ORD record
ord-b6c979fd37f34f83b3e62d6cd03ed819
Source dataset
uspto-grants-2016_02
Patent number
US09247740B2

Reaction notes

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