Dichloromethane → tert-Butyl 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoate

HRID 1257530Notes

Reaction equation

HRID 1257530 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]2[CH2:19][C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[O:17][N:16]=2)[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Br-].[CH3:27][C:28]1[CH:29]=[CH:30][C:31]([Zn+])=[N:32][CH:33]=1.[K+].[K+].[K+].C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O.ClCCl>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:27][C:28]1[CH:29]=[CH:30][C:31]([C:2]2[CH:3]=[C:4]([CH:12]=[C:13]([C:15]3[CH2:19][C@@H:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[O:17][N:16]=3)[CH:14]=2)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])=[N:32][CH:33]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62717Edetate TripotassiumHCID 58096179tert-butyl 3-bromo-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoateHCID 178427808HCID 178427808, compound

Product 1

HCID 66895837tert-Butyl 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoateYield 90.4%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of tert-butyl 3-bromo-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoate (19.95 g, 49.5 mmol) and bis(tri-tert-butylphosphine)palladium(0) (0.76 g, 1.48 mmol) in dioxane (247 mL) was added 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 198 mL, 99 mmol). The reaction mixture was heated to 75° C. After 1 h, the reaction was cooled to ambient temperature. Aqueous ethylenediaminetetraacetic acid tripotassium salt (0.4 M, 200 mL) and dichloromethane (200 mL) were added. The mixture was stirred for 15 min and the organic solvent was evaporated. The mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% ethyl acetate 98% ethyl acetate/methanol) gave the title compound (18.6 g). MS 416.1 (M+1).

Workup

  1. temperaturethe reaction was cooled to ambient temperature
  2. customthe organic solvent was evaporated
  3. extractionThe mixture was extracted with dichloromethane (3×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (100% ethyl acetate 98% ethyl acetate/methanol)

Sources & evidence

ORD record
ord-a0b70897865d482a814efc7fdc0b37bd
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

Loading…