Potassium Phosphate, Tribasic → HCID 67080359, compound

HRID 1021396Notes

Reaction equation

HRID 1021396 reaction equation
Br[C:2]1[CH:35]=[CH:34][C:5]([CH2:6][CH2:7][NH:8][C:9]([C:11]2[CH:33]=[CH:32][C:14]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:21][CH2:22][O:23]4)=[CH:18][C:17]=3[Cl:31])=[CH:13][CH:12]=2)=[O:10])=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P([CH:57]2[CH2:62][CH2:61]CCC2)C2CCCCC2)CCCCC1.C1(B(O)O)CC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[Cl:31][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:16]=1[O:15][C:14]1[CH:32]=[CH:33][C:11]([C:9](=[O:10])[NH:8][CH2:7][CH2:6][C:5]3[CH:34]=[CH:35][C:2]([CH:61]4[CH2:62][CH2:57]4)=[CH:3][CH:4]=3)=[CH:12][CH:13]=1)[O:23][CH2:22][CH2:21][CH:20]2[C:26]([O:28][CH2:29][CH3:30])=[O:27]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 67080410Ethyl 7-(4-(4-bromophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate

Product 1

HCID 67080359HCID 67080359, compoundYield 115.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a stirred suspension of ethyl 7-(4-(4-bromophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (0.56 g, 1.0 mmol) in toluene (6 mL) at ambient temperature was added successively water (0.3 mL), potassium phosphate (0.64 g, 3.0 mmol), tricyclohexylphosphine (0.11 g, 0.40 mmol), and cyclopropylboronic acid (0.17 g, 2.0 mmol). The resulting mixture was stirred and a balloon of nitrogen with a three-way purge valve was attached, and the flask was evacuated and refilled five times with nitrogen. Palladium(II) acetate (0.045 g, 0.20 mmol) was added, and again the flask was evacuated and refilled five times with nitrogen. The mixture was stirred in an oil bath set to 100° C. under the nitrogen balloon for 3 hours. The mixture was cooled to ambient temperature and diluted with ethyl acetate (25 mL) and water (15 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel, eluting with 70/30 hexanes/ethyl acetate, to afford ethyl 6-chloro-7-(4-(4-cyclopropylphenethylcarbamoyl)phenoxy)chroman-4-carboxylate as a white solid (0.24 g, 46% yield).

Workup

  1. customa balloon of nitrogen with a three-way purge valve
  2. customthe flask was evacuated
  3. additionrefilled five times with nitrogen
  4. customagain the flask was evacuated
  5. additionrefilled five times with nitrogen
  6. stirringThe mixture was stirred in an oil bath
  7. additiondiluted with ethyl acetate (25 mL) and water (15 mL)
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography on silica gel
  11. washeluting with 70/30 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-0e6daeb60dff4b1daf70d26f1f25782c
Source dataset
uspto-grants-2014_05
Patent number
US08716498B2

Reaction notes

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