Sodium Carbonate → HCID 59157621, compound

HRID 2422374Notes

Reaction equation

HRID 2422374 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:46](=O)([O-])[O-:47].[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][C:41]([O:47][CH3:46])=[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 59157621HCID 59157621, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 21881414Toluene isopropyl alcoholSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred slurry of 613 mg (1.17 mmol) of (S)-tert-butyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(6-bromo-pyridin-3-yl)propanoate and 422 mg (2.34 mmol, 2 eq.) of 2-ethylphenylboronic acid in 20 mL of 1:1 isopropanol/toluene was added 10.0 mL of 2 M aqueous sodium carbonate solution. The reaction mixture was purged twice with argon and evacuated and then 43.2 mg (0.059 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 9 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 (3:17) as eluant (5×15 cm column), gave the expected compound as a colorless oil, 401 mg, 59% 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-1b672d5f50d14d02aa667579da0e12fe
Source dataset
uspto-grants-2011_06
Patent number
US07960349B2

Reaction notes

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