Potassium Phosphate, Tribasic → HCID 86703534, compound

HRID 1849668Notes

Reaction equation

HRID 1849668 reaction equation
Cl[C:2]1[C:3]([O:16][CH2:17][C:18]23[CH2:27][CH:22]4[CH2:23][CH:24]([CH2:26][CH:20]([C:21]4([F:29])[F:28])[CH2:19]2)[CH2:25]3)=[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:30]1(B(O)O)[CH2:32][CH2:31]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:30]1([C:2]2[C:3]([O:16][CH2:17][C:18]34[CH2:19][CH:20]5[CH2:26][CH:24]([CH2:23][CH:22]([C:21]5([F:28])[F:29])[CH2:27]3)[CH2:25]4)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=2)[C:7]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])[CH2:32][CH2:31]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703533HCID 86703533, compound

Product 1

HCID 86703534HCID 86703534, compoundYield 66%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl 5-chloro-4-((4,4-difluoroadamantan-1-yl)methoxy)-2-fluorobenzoate (1.50 g, 3.48 mmol), cyclopropylboronic acid (0.45 g, 5.22 mmol), potassium phosphate (3.33 g, 15.7 mmol) and tricyclohexylphosphine tetrafluoroborate (0.13 g, 0.35 mmol) in toluene (60 mL) and water (3 mL) under a nitrogen atmosphere was added palladium acetate (0.08 g, 0.35 mmol). The reaction mixture was heated to 100° C. for 18 hours and then cooled to ambient temperature. Water (20 mL) was added and the mixture was filtered through a pad of diatomaceous earth and the solid was washed with ethyl acetate (150 mL). The organics were washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by crystallization (ethyl acetate and hexanes) afforded the title compound as colorless solid (1.00 g, 66%): 1H NMR (300 MHz, CDCl3) δ 7.42 (d, J=8.4 Hz, 1H), 6.47 (d, J=12.6 Hz, 1H), 3.57 (s, 2H), 2.29 (br s, 2H), 2.02-1.95 (m, 6H), 1.75-1.68 (m, 6H), 1.57 (s, 9H), 0.93-0.87 (m, 2H), 0.65-0.60 (m, 2H); MS (ES+) m/z 459.2 (M+23).

Workup

  1. temperaturecooled to ambient temperature
  2. filtrationthe mixture was filtered through a pad of diatomaceous earth
  3. washthe solid was washed with ethyl acetate (150 mL)
  4. washThe organics were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue
  8. customby crystallization (ethyl acetate and hexanes)

Sources & evidence

ORD record
ord-a89f82c9460e4ca4915e89f8b67d9a68
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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