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

HRID 1770645Notes

Reaction equation

HRID 1770645 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:10](/[C:28]([F:31])([F:30])[F:29])=[CH:11]\[C:12]([C:14]2[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[C:16]([CH3:27])[CH:15]=2)=O)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8].[NH2:32][OH:33].[OH-].[Cs+]>C(Cl)(Cl)Cl.O.ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@:10]2([C:28]([F:31])([F:30])[F:29])[O:33][N:32]=[C:12]([C:14]3[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[C:16]([CH3:27])[CH:15]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8]

Participants

7

Reactant 3

HCID 787HydroxylamineHCID 62750Cesium hydroxideHCID 86727021tert-butyl 4-[(E)-3-(3,5-dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoate

Product 1

HCID 86727020tert-butyl 4-[(5S)-5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoate

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

A 1500 mL reaction-vessel was charged at room temperature with 1-Anthracen-9-ylmethyl quininium chloride (2.93 g, 5.32 mmol) and tert-butyl 4-[(E)-3-(3,5-dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoate (12.7 g, 26.6 mmol) and dissolved in chloroform (700 mL). The mixture cooled down to −20° C. Then, a solution hydroxylamine (50 mass % in water, 3.3 mL) in water (16.7 mL) and cesium hydroxide (10.8 g, 71.8 mmol) in water (20 mL) were added simultaneously dropwise to the reaction mixture over 12 min. After the addition the reaction was kept 1.5 h at −20° 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 24.2 g of the crude title product. The product was purified over a silica gel column (eluent: EtOAc/Heptane) to obtain 12.6 gr of the title product.

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 24.2 g of the crude title product
  7. customThe product was purified over a silica gel column (eluent: EtOAc/Heptane)

Sources & evidence

ORD record
ord-e2f3541e388c4738ae8d27b2b6d93cc7
Source dataset
uspto-grants-2016_02
Patent number
US09247740B2

Reaction notes

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