Sodium Carbonate → HCID 86758103, compound

HRID 2184762Notes

Reaction equation

HRID 2184762 reaction equation
[Cl:1][C:2]1[S:6][C:5](B(O)O)=[CH:4][CH:3]=1.Br[C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:24])[CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[S:6][C:5]([C:11]2[CH:12]=[CH:13][C:14]([C:17](=[O:24])[CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])=[CH:15][CH:16]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 838865Methyl 4-(4-bromophenyl)-4-oxobutanoateHCID 27343245-Chlorothiophene-2-boronic acid2×

Product 1

HCID 86758103HCID 86758103, compoundYield 66.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A stirred mixture of 5-chloro-thiophene-2-boronic acid (5.15 g, 0.0317 mol), 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (8.00 g, 0.0294 mol), and tetrakis(triphenylphosphine)palladium(0) (1.09 g, 0.00094 mol) in a two-phase mixture of toluene (62 mL) and 2.0 M aqueous sodium carbonate (31 mL, 0.062 mol) was heated at 70° C. for 20 hours and allowed to cool to room temperature. Additional 5-chloro-thiophene-2-boronic acid (0.369 g, 0.00227 mol) was added, and the mixture was reheated at 65° C. for 20 hours. The mixture was cooled to room temperature and filtered through Celite, eluting with dichloromethane. Filtrate and washings were combined, and the mixture was washed with 0.10 M aqueous sodium hydroxide (100 mL), 3% aqueous ammonium hydroxide (100 mL), water, and brine. The organics were dried (Na2SO4), and rotary evaporated to a solid. The residue was dissolved in chloroform. silica gel (101 g, 230-400 mesh) was added, and the mixture was rotary evaporated to dryness. The residue was purified by chromatography on silica gel (1450 g, 230-400 mesh), eluting with hexanes-acetone (12:1, 16×1L; 9:1, 12×1L) to give 6.04 g of 4-[4-(5-chloro-thiophen-2-yl)-phenyl]-4-oxo-butyric acid, methyl ester as a bright yellow solid; mp 117-118° C.

Workup

  1. temperatureto cool to room temperature
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered through Celite
  4. washeluting with dichloromethane
  5. washthe mixture was washed with 0.10 M aqueous sodium hydroxide (100 mL), 3% aqueous ammonium hydroxide (100 mL), water, and brine
  6. dry with materialThe organics were dried (Na2SO4)
  7. customrotary evaporated to a solid
  8. dissolutionThe residue was dissolved in chloroform
  9. additionsilica gel (101 g, 230-400 mesh) was added
  10. customthe mixture was rotary evaporated to dryness
  11. customThe residue was purified by chromatography on silica gel (1450 g, 230-400 mesh)
  12. washeluting with hexanes-acetone (12:1, 16×1L; 9:1, 12×1L)

Sources & evidence

ORD record
ord-2310f07be11c454eaf604823438ea0a5
Source dataset
uspto-grants-2002_06
Patent number
US06399612B1

Reaction notes

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