Tributylphosphine → 4-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-3-methyl-butyl]-benzoic Acid Methyl Ester

HRID 2363209Notes

Reaction equation

HRID 2363209 reaction equation
[OH:1][CH:2]([C:7]1[CH:16]=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][CH:8]=1)[CH2:3][CH:4]([CH3:6])[CH3:5].N1CCCCC1.N1CCCCC1.N(C(O)=O)=NC(O)=O.C(P(CCCC)CCCC)CCC.[CH3:50][C:51]1[CH:56]=[C:55](O)[CH:54]=[C:53]([CH3:58])[C:52]=1[C:59]1[CH:64]=[CH:63][C:62]([C:65]([F:68])([F:67])[F:66])=[CH:61][CH:60]=1>C1(C)C=CC=CC=1.CO.CCOC(C)=O>[CH3:14][O:13][C:11](=[O:12])[C:10]1[CH:9]=[CH:8][C:7]([CH:2]([O:1][C:55]2[CH:56]=[C:51]([CH3:50])[C:52]([C:59]3[CH:64]=[CH:63][C:62]([C:65]([F:66])([F:68])[F:67])=[CH:61][CH:60]=3)=[C:53]([CH3:58])[CH:54]=2)[CH2:3][CH:4]([CH3:6])[CH3:5])=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 13831TributylphosphineHCID 569717492,6-Dimethyl-4'-(trifluoromethyl)-[1,1'-biphenyl]-4-olHCID 59518172Methyl 4-(1-hydroxy-3-methylbutyl)benzoate2×HCID 66707187Azodicarboxylate dipiperidine

Product 1

HCID 674859224-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-3-methyl-butyl]-benzoic Acid Methyl Ester

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Methyl 4-(1-hydroxy-3-methylbutyl)benzoate (44.00 g, 197.94 mmol) is dissolved in toluene (1.12 L) and the batch temperature is adjusted to 0° C. Solid azodicarboxylic acid dipiperidine (74.92 g, 296.92 mmol) is added to the reaction solution. Tri-n-butylphosphine (78.0 mL, 296.92 mmol) is added to the reaction solution drop-wise maintaining a batch temperature at 0° C. 2,6-Dimethyl-4′-(trifluoromethyl)biphenyl-4-ol (65.92 g, 237.53 mmol), dissolved in toluene (1 L), is added to the reaction drop-wise maintaining the batch temperature of 0° C. The reaction mixture is warmed to 25° C. and stirred approximately 16 h. The reaction is analyzed by TLC 30% EtOAc in hexanes. Product rf=0.63, carbinol rf=0.34, and the biaryl rf=0.39. The reaction is continued until no methyl 4-(1-hydroxy-3-methylbutyl)benzoate is observed by TLC. Upon reaction completion, the solvent is removed by vacuum distillation and replaced with hexane. The mixture is chromatographed using silica and is eluted with hexanes. The fractions, containing the product, are concentrated to 85.89 g (92.2%) of a viscous oil under reduced pressure at 45° C. 1H NMR (400 MHz, DMSO-d6): δ 7.92 (d, 2H), 7.72 (d, 2H), 7.55 (d, 2H), 7.29 (d, 2H), 6.68 (s, 2H), 5.44 (dd, 1H), 3.81 (s, 3H), 1.83 (m, 1H), 1.82 (s, 6H), 1.75 (m, 1H), 1.52 (m, 1H), 0.94 (dd, 6H).

Workup

  1. customis adjusted to 0° C
  2. additionis added to the reaction drop-wise
  3. temperaturemaintaining the batch temperature of 0° C
  4. temperatureThe reaction mixture is warmed to 25° C.
  5. customUpon reaction completion
  6. customthe solvent is removed by vacuum distillation
  7. customThe mixture is chromatographed
  8. washis eluted with hexanes
  9. additionThe fractions, containing the product
  10. concentrationare concentrated to 85.89 g (92.2%) of a viscous oil under reduced pressure at 45° C

Sources & evidence

ORD record
ord-41c328c8f56d45a7b7e830a3f8126d04
Source dataset
uspto-grants-2014_04
Patent number
US08691856B2

Reaction notes

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