Water → HCID 89701795, compound

HRID 2280676Notes

Reaction equation

HRID 2280676 reaction equation
CS([O:5][C@@H:6]1[CH2:10][CH2:9][O:8][CH2:7]1)(=O)=O.[F:11][C:12]1[C:13]([CH3:28])=[C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][OH:27])[CH:21]=2)[C:15]([CH3:19])=[CH:16][C:17]=1O.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[F:11][C:12]1[C:13]([CH3:28])=[C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][OH:27])[CH:21]=2)[C:15]([CH3:19])=[CH:16][C:17]=1[O:5][C@H:6]1[CH2:10][CH2:9][O:8][CH2:7]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 58248246HCID 58248246, compoundHCID 89701791HCID 89701791, compound

Product 1

HCID 89701795HCID 89701795, compoundYield 50.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

The crude (R)-tetrahydrofuran-3-yl methanesulfonate 1b (202 mg, 1.22 mmol), the crude 3-fluoro-3′-(hydroxymethyl)-2,6-dimethylbiphenyl-4-ol 19b (200 mg, 0.81 mmol) and cesium carbonate (527 mg, 1.62 mmol) were dissolved in 5 mL of N,N-dimethylformamide. The reaction mixture was heated to 80° C. and stirred for 12 hours. The resulting mixture was mixed with 20 mL of water and extracted with ethyl acetate (30 mL×2). The combined organic phase was washed with water (30 mL) and saturated sodium chloride solution (30 mL) successively, dried with anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with elution system B to obtain the title compound (S)-(3′-fluoro-2′,6′-dimethyl-4′-((tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methanol 19c (130 mg, yield 50.8%) as a colorless slime.

Workup

  1. extractionextracted with ethyl acetate (30 mL×2)
  2. washThe combined organic phase was washed with water (30 mL) and saturated sodium chloride solution (30 mL) successively
  3. dry with materialdried with anhydrous magnesium sulphate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography with elution system B

Sources & evidence

ORD record
ord-3c062bbccbee4ce3bcfea134c23f7eff
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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