Sodium Carbonate → HCID 59157624, compound

HRID 2422373Notes

Reaction equation

HRID 2422373 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([CH2:27][C:28]3[CH:29]=[N:30][C:31](Br)=[CH:32][CH:33]=3)[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH2:35]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1B(O)O)[CH3:36].C(=O)([O-])[O-].[Na+].[Na+]>C(O)(C)C.C1(C)C=CC=CC=1>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([CH2:27][C:28]3[CH:29]=[N:30][C:31]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=4[CH2:35][CH3:36])=[CH:32][CH:33]=3)[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 41008622-Ethylphenylboronic Acid (contains varying amounts of Anhydride)HCID 86609631HCID 86609631, compound

Product 1

HCID 59157624HCID 59157624, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 21881414Toluene isopropyl alcoholSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred slurry of 1.75 g (3.35 mmol) of (S)-tert-butyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(6-bromo-pyridin-3-yl)propanoate and 1.005 g (6.70 mmol, 2 eq.) of 2-ethylphenylboronic acid in 50 mL of 1:1 isopropanol/toluene was added 25.0 mL of 2 M aqueous sodium carbonate solution. The reaction mixture was purged twice with argon and evacuated and then 124 mg (0.167 mmol, 0.05 equivalents) of bis(tricyclohexylphosphine)palladium(II)chloride was added and the mixture was again purged with argon and evacuated. The rapidly stirred mixture was heated at 80° C. under argon. After 20 h, the reaction mixture was cooled to room temperature and partially concentrated to remove isopropanol. The residue was partitioned between ethyl acetate and water and the aqueous phase was extracted once more with ethyl acetate. The organic extracts were combined, dried over magnesium sulfate, filtered and concentrated to give a brown oil. Purification by chromatography on silica gel using ethyl acetate/dichloromethane (1:9) as eluant (5×15 cm column), gave the desired compound as a colorless oil, 1.25 g, 77% yield.

Workup

  1. customThe reaction mixture was purged twice with argon
  2. customevacuated
  3. customthe mixture was again purged with argon
  4. customevacuated
  5. temperaturethe reaction mixture was cooled to room temperature
  6. concentrationpartially concentrated
  7. customto remove isopropanol
  8. customThe residue was partitioned between ethyl acetate and water
  9. extractionthe aqueous phase was extracted once more with ethyl acetate
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a brown oil
  14. customPurification by chromatography on silica gel

Sources & evidence

ORD record
ord-48864bffcb9c4a348e05453c4e04cb18
Source dataset
uspto-grants-2011_06
Patent number
US07960349B2

Reaction notes

Loading…