Triphenylphosphine → (+/-)-5-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carboxylic acid ethyl ester

HRID 660981Notes

Reaction equation

HRID 660981 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([CH:11]([OH:13])[CH3:12])=[CH:9][CH:10]=1)=[O:5])[CH3:2].[CH3:14][C:15]1[CH:20]=[C:19](O)[CH:18]=[C:17]([CH3:22])[C:16]=1[C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1(C)C=CC=CC=1.CO>[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([CH:11]([O:13][C:19]2[CH:20]=[C:15]([CH3:14])[C:16]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:30])([F:32])[F:31])=[CH:25][CH:24]=3)=[C:17]([CH3:22])[CH:18]=2)[CH3:12])=[CH:9][CH:10]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 569717492,6-Dimethyl-4'-(trifluoromethyl)-[1,1'-biphenyl]-4-olHCID 59355961Ethyl 5-(1-hydroxyethyl)thiophene-2-carboxylate

Product 1

HCID 67485105(+/-)-5-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carboxylic acid ethyl esterYield 71%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

A mixture of (±)-5-(1-hydroxy-ethyl)-thiophene-2-carboxylic acid ethyl ester (0.402 g, 2.01 mmol), 2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-ol (0.593 g, 2.23 mmol), and PPh3 (0.798 g, 3.04 mmol) is dissolved in toluene (20 mL) and treated with 1,1′-(azodicarbonyl)dipiperidine (ADDP, 0.763 g, 3.02 mmol) and stirred overnight at rt. The mixture is diluted with MeOH until homogeneous and concentrated. The residue is loaded onto silica gel and eluted using hexanes with an ethyl acetate gradient from 0% to 40% giving (±)-5-[1-(2,6-Dimethyl-4′-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carboxylic acid ethyl ester (0.638 g, 71%) as a clear syrup. MS (ES): 447.3 [M−H]−.

Workup

  1. concentrationconcentrated
  2. washeluted

Sources & evidence

ORD record
ord-b65ea3a333374b1db8e8b4502ea79785
Source dataset
uspto-grants-2011_12
Patent number
US08084489B2

Reaction notes

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