Potassium Phosphate, Tribasic → HCID 86703751, compound

HRID 1849864Notes

Reaction equation

HRID 1849864 reaction equation
Cl[C:2]1[C:3]([O:16][CH2:17][CH:18]2[CH:23]([CH3:24])[CH2:22][CH2:21][CH2:20][CH:19]2[CH3:25])=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH:26]1(B(O)O)[CH2:28][CH2:27]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:26]1([C:2]2[C:3]([O:16][CH2:17][CH:18]3[CH:23]([CH3:24])[CH2:22][CH2:21][CH2:20][CH:19]3[CH3:25])=[CH:4][C:5]([F:15])=[C:6]([CH:14]=2)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:28][CH2:27]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703748HCID 86703748, compound

Product 1

HCID 86703751HCID 86703751, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of tert-butyl 5-chloro-4-((2,6-dimethylcyclohexyl)-methoxy)-2-fluorobenzoate (0.43 g, 1.16 mmol), cyclopropylboronic acid (0.14 g, 1.74 mmol), potassium phosphate (1.48 g, 7.00 mmol) and tricyclohexylphosphine tetrafluoroborate (0.085 g, 0.230 mmol) in toluene (5 mL) and water (0.5 mL) under a nitrogen atmosphere was added palladium acetate (0.04 g, 0.12 mmol). The reaction mixture was heated at 130° C. for 30 minutes in the microwave then cooled to ambient temperature. Water (20 mL) was added and the mixture extracted with ethyl acetate (3×10 mL), the combined organics were washed with brine; dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) afforded tert-butyl 5-cyclopropyl-4-((2,6-dimethylcyclohexyl)methoxy)-2-fluorobenzoate (0.43 g, 1.16 mmol) which was used directly into the next step. To a solution of this compound (0.43 g, 1.16 mmol) in dichloromethane (2 mL), was added trifluoroacetic acid (2 mL). The reaction mixture was stirred at 0° C. for 1 hour and then concentrated in vacuo. The residue was purified by column chromatography (0 to 30% ethyl acetate in hexanes) to afford the title compound (0.142 g, 38%). MS (ES−) m/z 319.2 (M−1).

Workup

  1. temperaturethen cooled to ambient temperature
  2. extractionthe mixture extracted with ethyl acetate (3×10 mL)
  3. washthe combined organics were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by column chromatography (5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e1e5be65bb25487cbddb5318bf084c6b
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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