Potassium Carbonate → (R)-2,2,2-Trifluoro-1-(3'-methoxy-[1,1'-biphenyl]-4-yl)ethan-1-ol

HRID 2098435Notes

Reaction equation

HRID 2098435 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([OH:13])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[CH3:14][O:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:10][C:9]([F:12])([F:11])[C@@H:8]([C:5]1[CH:6]=[CH:7][C:2]([C:20]2[CH:19]=[CH:18][CH:17]=[C:16]([O:15][CH3:14])[CH:21]=2)=[CH:3][CH:4]=1)[OH:13]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 12640349(1R)-1-(4-Bromophenyl)-2,2,2-trifluoroethan-1-ol

Product 1

HCID 25191338(R)-2,2,2-Trifluoro-1-(3'-methoxy-[1,1'-biphenyl]-4-yl)ethan-1-olYield 89.2%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a stirred solution of (R)-1-(4-bromophenyl)-2,2,2-trifluoroethanol (2, 69 g, 0.27 mol, >99% ee), 3-methoxy phenylboronic acid (Matrix, 51 g, 0.34 mol, 97% purity), and bis(triphenylphosphine)palladium(II) dichloride (0.95 g, 0.5% mol) in ethanol (560 ml) was added a solution of potassium carbonate (112 g, 0.81 mol) in water (140 ml) under nitrogen. The resulting mixture was heated at 75° C. for 1 hour and deemed complete by GC-MS or TLC. After reaction mixture was cooled to 40° C., it was filtered through a pad of Celite, washed with methanol (3×100 ml). The filtrate was diluted with 100 ml of water and concentrated. The resulting syrup was dissolved in 700 ml of ethyl acetate and washed with 1 N sodium hydroxide (2×100 ml), water (2×100 ml) and brine (1×100 ml). The organic layer was heated with activated carbon (14 g) and Hyflo Super Cel (14 g) at 60° C. for 1 hours. This mixture was filtered hot and washed with ethyl acetate (100 ml) and then concentrated to a syrup. This syrup was immediately dissolved in 1% ethyl acetate/heptane (700 ml) and stirred for 4 hours. The resulting slurry was filtered and dried to give the titled compound as a white crystalline solid (3, 68 g, 89% yield, >99% ee)

Workup

  1. customAfter reaction mixture
  2. temperaturewas cooled to 40° C.
  3. filtrationit was filtered through a pad of Celite
  4. washwashed with methanol (3×100 ml)
  5. additionThe filtrate was diluted with 100 ml of water
  6. concentrationconcentrated
  7. dissolutionThe resulting syrup was dissolved in 700 ml of ethyl acetate
  8. washwashed with 1 N sodium hydroxide (2×100 ml), water (2×100 ml) and brine (1×100 ml)
  9. temperatureThe organic layer was heated with activated carbon (14 g) and Hyflo Super Cel (14 g) at 60° C. for 1 hours
  10. filtrationThis mixture was filtered hot
  11. washwashed with ethyl acetate (100 ml)
  12. concentrationconcentrated to a syrup
  13. dissolutionThis syrup was immediately dissolved in 1% ethyl acetate/heptane (700 ml)
  14. filtrationThe resulting slurry was filtered
  15. customdried

Sources & evidence

ORD record
ord-e120a375eb674f80b1dd95225da5f495
Source dataset
uspto-grants-2013_05
Patent number
US08450532B2

Reaction notes

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