Triisopropyl borate → (5-(Cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)boronic acid

HRID 1988899Notes

Reaction equation

HRID 1988899 reaction equation
[CH:1]1([NH:4][C:5](=[O:15])[C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8](I)[CH:7]=2)[CH2:3][CH2:2]1.[H-].[Na+].C([Li])CCC.[B:23](OC(C)C)([O:28]C(C)C)[O:24]C(C)C>O1CCCC1.O>[CH:1]1([NH:4][C:5]([C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]([B:23]([OH:28])[OH:24])[CH:7]=2)=[O:15])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 21531Triisopropyl borateHCID 24758Sodium hydrideHCID 21914570N-Cyclopropyl-3-fluoro-5-iodo-4-methylbenzamide2×HCID 178418339Butyllithium

Product 1

HCID 21914527(5-(Cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)boronic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

N-Cyclopropyl-5-fluoro-3-iodo-4-methylbenzamide (Intermediate 63) (5 g) in tetrahydrofuran (75 ml) was cooled to 0° C. then treated with sodium hydride (60% oil dispersion, 1.23 g) portionwise over 10 minutes. Once effervescence had ceased the reaction was cooled to −75° C. and n-butyl lithium (1.6M in hexanes, 20 ml) was added over 25 min maintaining a temperature of <−70° C. Triisopropyl borate (8 ml) was added over 10 min and the mixture was stirred at −70° C. for 4 h. Water (20 ml) was added and the mixture was allowed to warm to 5° C. The solvent was removed under vacuum and the residue was partitioned between saturated aqueous ammonium chloride and ethyl acetate. The organic phase was washed with saturated aqueous ammonium chloride and brine, dried (Na2SO4) and concentrated under vacuum. The residue was dissolved in dichloromethane/ethyl acetate and purified by column chromatography on silica eluting with dichloromethane:ethyl acetate (95:5 to 0:100) then methanol to give the title compound.

Workup

  1. temperaturemaintaining a temperature of <−70° C
  2. temperatureto warm to 5° C
  3. customThe solvent was removed under vacuum
  4. customthe residue was partitioned between saturated aqueous ammonium chloride and ethyl acetate
  5. washThe organic phase was washed with saturated aqueous ammonium chloride and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under vacuum
  8. dissolutionThe residue was dissolved in dichloromethane/ethyl acetate
  9. custompurified by column chromatography on silica eluting with dichloromethane:ethyl acetate (95:5 to 0:100)

Sources & evidence

ORD record
ord-fcb4d5c2fd644cdebba17399bee385b5
Source dataset
uspto-grants-2010_01
Patent number
US07642276B2

Reaction notes

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