Dimethyl Sulfoxide → Tert-butyl 2-hydroxy-6-[({4'-[2-hydroxy-1-(methoxycarbonyl)ethyl]-1,1'-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate

HRID 2076651Notes

Reaction equation

HRID 2076651 reaction equation
[CH3:1]S(C)=O.[CH2:5]=[O:6].[C:7](=[O:10])([O-])[OH:8].[Na+].[OH:12][C:13]1[C:25]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:23]=[C:22]([CH2:30][O:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][C:41]([CH2:44][C:45]([O:47][CH3:48])=[O:46])=[CH:40][CH:39]=3)=[CH:34][CH:33]=2)[C:14]=1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]>C(OCC)(=O)C>[OH:12][C:13]1[C:25]([C:26]([F:28])([F:29])[F:27])=[CH:24][CH:23]=[C:22]([CH2:30][O:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][C:41]([CH:44]([C:45]([O:47][CH3:48])=[O:46])[CH2:7][OH:8])=[CH:40][CH:39]=3)=[CH:34][CH:33]=2)[C:14]=1[C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16].[OH:12][C:13]1[C:25]([C:26]([F:28])([F:29])[F:27])=[CH:24][CH:23]=[C:22]([CH2:30][O:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][C:41]([C:44]([C:45]([O:47][CH3:48])=[O:46])=[CH2:1])=[CH:40][CH:39]=3)=[CH:34][CH:33]=2)[C:14]=1[C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16].[OH:12][C:13]1[C:25]([C:26]([F:28])([F:29])[F:27])=[CH:24][CH:23]=[C:22]([CH2:30][O:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][C:41]([C:44]([CH2:7][OH:10])([C:45]([O:47][CH3:48])=[O:46])[CH2:5][OH:6])=[CH:40][CH:39]=3)=[CH:34][CH:33]=2)[C:14]=1[C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16]

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 67119193HCID 67119193, compound

Product 3

HCID 67119106Tert-butyl 2-hydroxy-6-[({4'-[1-(methoxycarbonyl)vinyl]-1,1'-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoateYield 9%HCID 67119108Tert-butyl 2-hydroxy-6-[({4'-[2-hydroxy-1-hydroxymethyl-1-(methoxycarbonyl)ethyl]-1,1'-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoateYield 25%HCID 67119119Tert-butyl 2-hydroxy-6-[({4'-[2-hydroxy-1-(methoxycarbonyl)ethyl]-1,1'-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoateYield 58%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Dimethyl sulfoxide (3 ml), paraformaldehyde (90% purity, 300 mg) and sodium hydrogencarbonate (300 mg, 3.57 mmol) were added to tert-butyl 2-hydroxy-6-[({4′-[(methoxycarbonyl)methyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate (400 mg, 0.77 mmol) obtained in Example (6-9), and the mixture was stirred at 60° C. for 3 hours. After the reaction mixture was cooled to room temperature, it was diluted with ethyl acetate. The organic layer was successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=4/1-1/3) to give tert-butyl 2-hydroxy-6-[({4′-[2-hydroxy-1-(methoxycarbonyl)ethyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate as a colorless solid (246 mg, yield: 58%), tert-butyl 2-hydroxy-6-[({4′-[1-(methoxycarbonyl)vinyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate (37 mg, yield: 9%) and tert-butyl 2-hydroxy-6-[({4′-[2-hydroxy-1-hydroxymethyl-1-(methoxycarbonyl)ethyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate (112 mg, yield: 25%).

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. washThe organic layer was successively washed with water
  3. dry with materiala saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
  4. customThe residue obtained
  5. customby removing the solvent under reduced pressure
  6. customwas purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=4/1-1/3)

Sources & evidence

ORD record
ord-d412cc83c9d84c65895fafcc1aa2b3d8
Source dataset
uspto-grants-2011_04
Patent number
US07923573B2

Reaction notes

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