Potassium Phosphate, Tribasic → HCID 67081068, compound

HRID 1021562Notes

Reaction equation

HRID 1021562 reaction equation
[CH3:1][O:2][C:3]1[CH:34]=[C:33](Br)[CH:32]=[CH:31][C:4]=1[CH2:5][CH2:6][NH:7][C:8]([C:10]1[CH:30]=[CH:29][C:13]([O:14][C:15]2[CH:24]=[C:23]3[C:18]([CH:19]([C:25]([O-:27])=[O:26])[CH2:20][CH2:21][O:22]3)=[CH:17][C:16]=2[Cl:28])=[CH:12][CH:11]=1)=[O:9].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P([CH:57]2[CH2:62][CH2:61]CCC2)C2CCCCC2)CCCCC1.[CH:63]1(B(O)O)C[CH2:64]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:1][O:2][C:3]1[CH:34]=[C:33]([CH:61]2[CH2:62][CH2:57]2)[CH:32]=[CH:31][C:4]=1[CH2:5][CH2:6][NH:7][C:8]([C:10]1[CH:30]=[CH:29][C:13]([O:14][C:15]2[CH:24]=[C:23]3[C:18]([CH:19]([C:25]([O:27][CH2:63][CH3:64])=[O:26])[CH2:20][CH2:21][O:22]3)=[CH:17][C:16]=2[Cl:28])=[CH:12][CH:11]=1)=[O:9]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 86653238HCID 86653238, compound

Product 1

HCID 67081068HCID 67081068, compoundYield 165.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a stirred suspension of 7-(4-(2-methoxy-4-bromophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (130 mg; 0.22 mmol) in 2 mL toluene was added successively 0.1 mL water, potassium phosphate (141 mg; 0.66 mmol), tricyclohexylphosphine (25 mg; 0.08 mmol), and cyclopropylboronic acid (38 mg; 0.44 mmol) at ambient temperature with stirring. 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 (10 mg; 0.04 mmol) was added, and again the flask was evacuated and refilled five times with nitrogen. The mixture was then stirred in an oil bath set to 100° C. under the nitrogen balloon. After 3.5 hours the mixture was cooled to ambient temperature, and the reaction was determined to be complete by thin layer chromatography (50/50 hexane/EtOAc). The mixture was diluted with 10 mL EtOAc and 5 mL water. The mixture was transferred to a separatory funnel and after shaking, the organic layer was dried over sodium sulfate and evaporated to give a brown oil. The crude material was purified by silica gel chromatography on a Biotage 25S column, eluting with 75/25 hexane/EtOAc to give 73 mg of ethyl 7-(4-(2-methoxy-4-cyclopropylphenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate as a colorless oil. MS (apci, pos) m/z=550.

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 then stirred in an oil bath
  7. customset to 100° C. under the nitrogen balloon
  8. additionThe mixture was diluted with 10 mL EtOAc and 5 mL water
  9. customThe mixture was transferred to a separatory funnel
  10. stirringafter shaking
  11. dry with materialthe organic layer was dried over sodium sulfate
  12. customevaporated
  13. customto give a brown oil
  14. customThe crude material was purified by silica gel chromatography on a Biotage 25S column
  15. washeluting with 75/25 hexane/EtOAc

Sources & evidence

ORD record
ord-43f477141c5448048d897952c2ee3c9b
Source dataset
uspto-grants-2014_05
Patent number
US08716498B2

Reaction notes

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