Sodium Carbonate → HCID 68807404, compound

HRID 1796227Notes

Reaction equation

HRID 1796227 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](=[O:23])[NH:14][C:15]1[CH:20]=[CH:19][C:18](Br)=[CH:17][C:16]=1[F:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][S:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](=[O:23])[NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[S:25][CH3:24])=[CH:17][C:16]=1[F:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27735432-(Methylthio)benzeneboronic acidHCID 68805934HCID 68805934, compound

Product 1

HCID 68807404HCID 68807404, compound

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

2-(4-Bromo-2-fluoro-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (2 g, 4.8 mmol), 2-(methylthio)benzene boronic acid (0.98 g, 5.8 mmol), and tetrabutylammonium bromide (78 mg, 0.24 mmol) were combined in 30 mL toluene, added 5 mL of a 2M aqueous Na2CO3 solution followed by tetrakistriphenylphosphine palladium(0) (0.28 g, 0.24 mmol). Heated reaction at reflux for 4 hours, cooled, concentrated, redissolved in EtOAc (250 mL), washed with water (3×200 mL), brine (200 mL), dried with MgSO4, filtered, and concentrated in the presence of 4 g coarse silica. Loaded silica onto a silica gel column, eluted with 20% EtOAc in hexanes. Combined and concentrated pure fractions to yield title compound as a yellow foam. (1.84 g, 88%) APCI (AP−): 429.2 (M−H)−.

Workup

  1. temperatureHeated
  2. customreaction
  3. temperatureat reflux for 4 hours
  4. temperaturecooled
  5. concentrationconcentrated
  6. dissolutionredissolved in EtOAc (250 mL)
  7. washwashed with water (3×200 mL), brine (200 mL)
  8. dry with materialdried with MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in the presence of 4 g coarse silica
  11. washLoaded silica onto a silica gel column, eluted with 20% EtOAc in hexanes
  12. concentrationconcentrated pure fractions

Sources & evidence

ORD record
ord-cb777c385db74665aed8bbe8b0cc86cc
Source dataset
uspto-grants-2006_04
Patent number
US07030141B2

Reaction notes

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