Triphenylphosphine → 4-((4-Bromo-3-chlorophenoxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)-isoxazole

HRID 2280865Notes

Reaction equation

HRID 2280865 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[Br:8].[CH:10]1([C:13]2[O:17][N:16]=[C:15]([C:18]3[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:25])[C:14]=2[CH2:26]O)[CH2:12][CH2:11]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1.C(Cl)Cl>[Br:8][C:7]1[CH:6]=[CH:5][C:4]([O:9][CH2:26][C:14]2[C:15]([C:18]3[C:19]([Cl:25])=[CH:20][CH:21]=[CH:22][C:23]=3[Cl:24])=[N:16][O:17][C:13]=2[CH:10]2[CH2:12][CH2:11]2)=[CH:3][C:2]=1[Cl:1]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 70181824-Bromo-3-chlorophenolHCID 45790382(5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methanol

Product 1

HCID 712054084-((4-Bromo-3-chlorophenoxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)-isoxazole

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

3-Chloro-4-bromophenol (3.8 g, 18.3 mmol) was mixed with (5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methanol (3.47 g, 12.2 mmol) and triphenylphosphine (6.41 g, 24.4 mmol) in toluene (150 mL). The mixture was cooled in an ice-bath and DIAD (4.8 mL, 24.4 mmol) as a solution in toluene (10 mL) was added drop-wise. The reaction was stirred at rt for 21 h and the solvents were removed on a rotavap leaving a yellow oily residue. This was dissolved in DCM (200 mL), silica (˜20 g) was added and the mixture was evaporated to dryness. This material was loaded on the top of a silica column and purified eluting with hexanes/MTBE 9:1. The product containing fractions were pooled and the solvent removed under reduced pressure, leaving pure product 8e as a colourless oil that crystallized upon drying under vacuum overnight. Yield: 5.07 g (88%). 1H-NMR (CDCl3), δ (ppm): 7.45-7.30 (m, 4H), 6.90 (s, 1H), 6.60-6.55 (m, 1H), 2.15-2.07 (m, 1H), 1.32-1.25 (m, 2H), 1.20-1.11 (m, 2H).

Workup

  1. temperatureThe mixture was cooled in an ice-bath
  2. customthe solvents were removed on a rotavap
  3. customleaving a yellow oily residue
  4. additionsilica (˜20 g) was added
  5. customthe mixture was evaporated to dryness
  6. custompurified
  7. washeluting with hexanes/MTBE 9:1
  8. additionThe product containing fractions
  9. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-078910fbb11c4f10a80989413279be67
Source dataset
uspto-grants-2015_09
Patent number
US09139539B2

Reaction notes

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