1,2-Dimethoxyethane → HCID 86670310, compound

HRID 1972366Notes

Reaction equation

HRID 1972366 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[F:17][C:18]([F:41])([F:40])[C:19]([C:25]1[CH:30]=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][CH:26]=1)([OH:24])[C:20]([F:23])([F:22])[F:21].C(=O)([O-])[O-].[K+].[K+].COCCOC>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CO.O>[F:17][C:18]([F:40])([F:41])[C:19]([C:25]1[CH:26]=[CH:27][C:28]([C:2]2[CH:7]=[CH:6][C:5]([S:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)(=[O:10])=[O:9])=[CH:4][CH:3]=2)=[CH:29][CH:30]=1)([OH:24])[C:20]([F:21])([F:23])[F:22]

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 89970Benzene, 1-bromo-4-(phenylsulfonyl)- (9CI)HCID 591663151,1,1,3,3,3-Hexafluoro-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ol

Product 1

HCID 86670310HCID 86670310, compoundYield 41.9%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A 100 mL pressure vessel was charged with 1-bromo-4-(phenylsulfonyl)benzene (1.00 g, 3.37 mmol, Example 17, step 1), 1,1,1,3,3,3-hexafluoro-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-propanol (1.62 g, 4.37 mmol), potassium carbonate (1.40 g, 10.10 mmol), tetrakis(triphenylphosphine)palladium (0) (0.194 g, 0.168 mmol), 20 mL of 1,2-dimethoxyethane, and 5 mL of water. The vessel was sealed and the reaction was heated to 100° C. for 2 h. After cooling to room temperature, the mixture was diluted with EtOAc (30 mL), separated, dried (MgSO4) and concentrated to give an oil. Purification via column chromatography (40 g of silica, 0 to 50% EtOAc in hexanes) produced a yellow solid that was slurried with cold (0° C.) MeOH (25 mL) to give 1,1,1,3,3,3-hexafluoro-2-(4′-(phenylsulfonyl)-4-biphenylyl)-2-propanol (0.650 g). 1H NMR (400 MHz, CD3OD) δ 8.08-7.95 (m, 4H), 7.91-7.74 (m, 6H), 7.69-7.54 (m, 3H). m/z (ESI, +ve ion) 461.0 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=1.66 μM; GK-GKRP EC50 (LC MS/MS)=3.96 μM.

Workup

  1. customThe vessel was sealed
  2. temperatureAfter cooling to room temperature
  3. customseparated
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto give an oil
  7. customPurification via column chromatography (40 g of silica, 0 to 50% EtOAc in hexanes)
  8. customproduced a yellow solid

Sources & evidence

ORD record
ord-39dae0de37654d17afc86748e7b3de06
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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