Sodium Carbonate → HCID 68805882, compound

HRID 1796264Notes

Reaction equation

HRID 1796264 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:10][C@@H:9]1[C:21](=[O:31])[NH:22][C:23]1[CH:28]=[CH:27][C:26](Br)=[CH:25][C:24]=1[F:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:32][S:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:10][C@@H:9]1[C:21](=[O:31])[NH:22][C:23]1[CH:28]=[CH:27][C:26]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[S:33][CH3:32])=[CH:25][C:24]=1[F:30])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27735432-(Methylthio)benzeneboronic acidHCID 68806399HCID 68806399, compound

Product 1

HCID 68805882HCID 68805882, compound

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2R,4R)-2-(4-Bromo-2-fluoro-phenylcarbamoyl)-4-(tert-butyl-dimethyl-silanyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (5.7 g, 10 mmol), 2-(methylthio)benzene boronic acid (2.1 g, 12.6 mmol), and tetrabutylammonium bromide (0.17 g, 0.52 mmol) were combined in 50 mL toluene, added 10 mL of a 2M aqueous Na2CO3 solution followed by tetrakistriphenylphosphine palladium(0) (0.61 g, 0.52 mmol). Heated reaction at reflux for 4 hours, cooled, dissolved in EtOAc (250 mL), washed with water (200 mL), brine, dried with MgSO4, filtered, and concentrated in the presence of 15 g coarse silica. Slurried silica in mobile phase and loaded onto a silica gel column, eluted with 25% EtOAc in hexanes. Combined and concentrated fractions to yield title compound. (4.1 g, 70%) APCI (AP−): 559.3 (M−H)−.

Workup

  1. temperatureHeated
  2. customreaction
  3. temperatureat reflux for 4 hours
  4. temperaturecooled
  5. washwashed with water (200 mL), brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in the presence of 15 g coarse silica
  9. washeluted with 25% EtOAc in hexanes
  10. concentrationconcentrated fractions

Sources & evidence

ORD record
ord-8122e11a0bd4495987fd05a9834a4e24
Source dataset
uspto-grants-2006_04
Patent number
US07030141B2

Reaction notes

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