Ethyl Acetate → 2',6'-Dimethyl-4'-(3-(methylsulfonyl)propoxy)(1,1'-biphenyl)-3-methanol

HRID 1848803Notes

Reaction equation

HRID 1848803 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([O:9][CH2:10][CH2:11][CH2:12][S:13]([CH3:16])(=[O:15])=[O:14])=[CH:4][C:3]=1[CH3:17].[OH:18][CH2:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:17][C:3]1[CH:4]=[C:5]([O:9][CH2:10][CH2:11][CH2:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH:6]=[C:7]([CH3:8])[C:2]=1[C:24]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:19][OH:18])[CH:25]=1

Participants

10

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 709269352-Bromo-1,3-dimethyl-5-[3-(methylsulfonyl)propoxy]benzene

Product 1

HCID 593425562',6'-Dimethyl-4'-(3-(methylsulfonyl)propoxy)(1,1'-biphenyl)-3-methanolYield 82.3%

Reagents, catalysts & solvents 5

HCID 11776TriphenylphosphineCatalystHCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Bromo-1,3-dimethyl-5-[3-(methylsulfonyl)propoxy]benzene (1.0 g), 3-hydroxymethylphenylboronic acid (0.497 g, 1.05 eq), triphenylphosphine (65.3 mg, 0.08 eq) and tetrabutylammonium bromide (50.2 mg, 0.05 eq) were dissolved in tetrahydrofuran (12 mL). Tripotassium phosphate (1.98 g, 3 eq) dissolved in water (5 mL) was added, and palladium acetate (14.0 mg) was added under a nitrogen atmosphere. The mixture was stirred under heated reflux for 8 hr. To the reaction mixture was added ethyl acetate (12 mL), and the insoluble material was removed. The filtrate was partitioned, and the organic layer was washed with 10% brine. After treatment with activated carbon, ethanol was added, and the mixture was concentrated is under reduced pressure. To the obtained oil was added ethyl acetate (3 mL), and the oil was dissolved. n-Heptane (10 mL) was added to allow crystallization. The obtained crystals were collected by filtration, and dried to give the title compound (0.893 g).

Workup

  1. additionwas added
  2. temperatureunder heated
  3. temperaturereflux for 8 hr
  4. customthe insoluble material was removed
  5. customThe filtrate was partitioned
  6. washthe organic layer was washed with 10% brine
  7. additionAfter treatment with activated carbon, ethanol was added
  8. concentrationthe mixture was concentrated
  9. additionTo the obtained oil was added ethyl acetate (3 mL)
  10. dissolutionthe oil was dissolved
  11. additionn-Heptane (10 mL) was added
  12. customcrystallization
  13. filtrationThe obtained crystals were collected by filtration
  14. customdried

Sources & evidence

ORD record
ord-844c8663aace43369b71a148e5b07d9b
Source dataset
uspto-grants-2015_02
Patent number
US08952185B2

Reaction notes

Loading…