1,2-Dimethoxyethane → HCID 57665952, compound

HRID 889748Notes

Reaction equation

HRID 889748 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[CH:5]([C:10]1[CH:11]=[C:12]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)[CH:13]=[C:14](OS(C(F)(F)F)(=O)=O)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2].[N:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1.COCCOC.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:34])[CH:5]([C:10]1[CH:11]=[C:12]([C:24]2[CH:25]=[CH:26][C:27]([C:30]([F:32])([F:33])[F:31])=[CH:28][CH:29]=2)[CH:13]=[C:14]([C:38]2[CH:39]=[CH:40][N:35]=[CH:36][CH:37]=2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2]

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 577550554-Methyl-2-(5-trifluoromethanesulfonyloxy-4'-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester

Product 1

HCID 57665952HCID 57665952, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 4-methyl-2-(5-trifluoromethanesulfonyloxy-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester (1g) (2.0 g, 3.90 mol), pyridine-4-boronic acid (540 mg, 4.39 mol), 1,2-dimethoxyethane (8 mL) and aqueous Na2CO3 (2 M, 1.93 mL, 3.90 mol) was mechanically stirred while purging N2 at room temperature for 10 min. To this system was added Pd(Ph3)4 (75 mg, 0.06 mmol) and heated to reflux (95° C.) for 2 h. Added another portion of Pd(Ph3)4 (75 mg, 0.06 mmol) and heated to reflux (95° C.) for further 2 h. The red-brown mixture was diluted with EtOAc (25 mL) and washed with saturated aqueous NaHCO3 solution (3×50 mL) and brine (2×50 mL). The organic fraction was dried (Na2SO4) and concentrated in vacuo. The crude mixture was purified by ISCO column chromatography to obtain 4-methyl-2-(5-pyridin-4-yl-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester.

Workup

  1. customwhile purging N2 at room temperature for 10 min
  2. temperatureheated
  3. temperatureheated
  4. temperatureto reflux (95° C.) for further 2 h
  5. washwashed with saturated aqueous NaHCO3 solution (3×50 mL) and brine (2×50 mL)
  6. dry with materialThe organic fraction was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude mixture was purified by ISCO column chromatography

Sources & evidence

ORD record
ord-1ed79fe1d29944f4aff9a0f1995c1d24
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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