3-(3-Bromophenyl)cyclobutan-1-one → 3-(3-Bromophenyl)-1-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)cyclobutanol

HRID 2280855Notes

Reaction equation

HRID 2280855 reaction equation
Br[C:2]1[CH:25]=[CH:24][C:5]([O:6][CH2:7][C:8]2[C:9]([C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:23])=[N:10][O:11][C:12]=2[CH:13]2[CH2:15][CH2:14]2)=[CH:4][C:3]=1[Cl:26].[Li]CCCC.[Br:32][C:33]1[CH:34]=[C:35]([CH:39]2[CH2:42][C:41](=[O:43])[CH2:40]2)[CH:36]=[CH:37][CH:38]=1>C1COCC1>[Br:32][C:33]1[CH:34]=[C:35]([CH:39]2[CH2:40][C:41]([C:2]3[CH:25]=[CH:24][C:5]([O:6][CH2:7][C:8]4[C:9]([C:16]5[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=5[Cl:23])=[N:10][O:11][C:12]=4[CH:13]4[CH2:14][CH2:15]4)=[CH:4][C:3]=3[Cl:26])([OH:43])[CH2:42]2)[CH:36]=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 177501013-(3-Bromophenyl)cyclobutan-1-oneHCID 712054084-((4-Bromo-3-chlorophenoxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)-isoxazoleHCID 178418339Butyllithium

Product 1

HCID 712054233-(3-Bromophenyl)-1-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)cyclobutanolYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of compound 1a (14 g, 29.6 mmol) in dry THF (500 ml) at −78° C. was added dropwise n-BuLi (18.5 mL, 1.6 M in hexane, 29.6 mmol). The mixture was stirred for an additional 1 h at −78° C. and a solution of compound 2a (6.5 g, 28.9 mmol) in dry THF (50 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 1 h and then warmed to rt and quenched with saturated aq. NH4Cl (500 mL). The mixture was extracted with EA (500 mL×2), the combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by CC (EA/PE=1:5) to give the title compound 2b (6.5 g, 37%) as a white solid.

Workup

  1. stirringThe resulting mixture was stirred at −78° C. for 1 h
  2. temperaturewarmed to rt
  3. customquenched with saturated aq. NH4Cl (500 mL)
  4. extractionThe mixture was extracted with EA (500 mL×2)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by CC (EA/PE=1:5)

Sources & evidence

ORD record
ord-51d921374f60498b87b802eb5e9671a0
Source dataset
uspto-grants-2015_09
Patent number
US09139539B2

Reaction notes

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