Potassium Phosphate, Tribasic → HCID 87426355, compound

HRID 623520Notes

Reaction equation

HRID 623520 reaction equation
Br[C:2]1[C:3]([O:12][CH2:13][CH:14]([F:16])[F:15])=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH:17]1(B(O)O)[CH2:19][CH2:18]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:17]1([C:2]2[C:3]([O:12][CH2:13][CH:14]([F:16])[F:15])=[N:4][CH:5]=[C:6]([CH:11]=2)[C:7]([O:9][CH3:10])=[O:8])[CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 87426398HCID 87426398, compound

Product 1

HCID 87426355HCID 87426355, compoundYield 81.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22272177Toluene waterSolvent

Procedure

A mixture of methyl 5-bromo-6-(2,2-difluoroethoxy)nicotinate (900 mg, 3.0 mmol, Step-2 of Amine-74), cyclopropylboronic acid (780 mg, 9.1 mmol), palladium(II) acetate (34 mg, 0.15 mmol), tricyclohexylphosphine (0.60 mL, 0.30 mmol, 0.5M in toluene) and potassium phosphate (1.6 g, 7.6 mmol) in toluene/water (10:1, 33 mL) is stirred at reflux temperature overnight. After cooled to room temperature, the mixture is filtered through a pad of celite, washed with ethyl acetate. The filtrate is extracted with ethyl acetate and dried over sodium sulfate. The organic solvent is removed under reduced pressure and then the residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (15:1) to give 630 mg (81% yield) of the title compound as a pale yellow solid.

Workup

  1. temperatureat reflux temperature overnight
  2. filtrationthe mixture is filtered through a pad of celite
  3. washwashed with ethyl acetate
  4. extractionThe filtrate is extracted with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. customThe organic solvent is removed under reduced pressure
  7. customthe residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (15:1)

Sources & evidence

ORD record
ord-96b9f23fe5b4412db595ca9bf608da10
Source dataset
uspto-grants-2016_04
Patent number
US09302991B2

Reaction notes

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