Hydrochloric Acid → 5-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-fluorobenzonitrile

HRID 1848324Notes

Reaction equation

HRID 1848324 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:22]([F:25])([F:24])[F:23])=[CH:10][C:11]([C:13]2[CH:14]=[CH:15][C:16]([F:21])=[C:17]([CH:20]=2)[C:18]#[N:19])=O)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[OH-:26].[Na+].Cl.[NH2:29]O.Cl>C1(C)C=CC=CC=1.O.CN1CCCC1=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:22]([F:25])([F:24])[F:23])[O:26][N:29]=[C:11]([C:13]3[CH:14]=[CH:15][C:16]([F:21])=[C:17]([CH:20]=3)[C:18]#[N:19])[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 866421895-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-2-butenoyl)-2-fluorobenzonitrile

Product 1

HCID 716156875-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-fluorobenzonitrileYield 92.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 1140TolueneSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

2.50 g of toluene and 1.50 g of N-methyl-2-pyrrolidone were added to 0.50 g (1.29 mmol) of 5-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-2-butenoyl)-2-fluorobenzonitrile, and the mixture was cooled to 0° C. After adding in dropwise to this mixture the solution which was prepared by adding 0.52 g of water to 0.21 g (5.16 mmol) of sodium hydroxide, and then adding the solution in which 0.099 g (1.42 mmol) of hydroxylamine hydrochloride was dissolved into 0.21 g of water in dropwise, the mixture was stirred for 2 hours at 0° C. The aqueous solution which was prepared from 0.81 g (7.74 mmol) of 35% hydrochloric acid and 2.42 g of water was added in dropwise to the reaction solution, and the mixture was stirred for 1 hour. 10 ml of toluene was added and separation operation was performed. The toluene phase was washed twice with 5 ml of water. The solvent was distilled off under reduced pressure to obtain 0.48 g of 5-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-fluorobenzonitrile (yield 92.9%).

Workup

  1. additionAfter adding in dropwise to this mixture the solution which
  2. customwas prepared
  3. additionwas added in dropwise to the reaction solution
  4. stirringthe mixture was stirred for 1 hour
  5. customseparation operation
  6. washThe toluene phase was washed twice with 5 ml of water
  7. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-cba705fe5b2a42d4a49b3d84e58a8a03
Source dataset
uspto-grants-2015_02
Patent number
US08952175B2

Reaction notes

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