Tributylphosphine → 3-(2-Methyl-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-yl]-ethoxy}-phenyl)-propionic acid methyl ester

HRID 860665Notes

Reaction equation

HRID 860665 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[O:5][C:6]=1[CH:7]([OH:9])[CH3:8].[CH3:20][O:21][C:22](=[O:33])[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28](O)=[CH:27][C:26]=1[CH3:32].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1(C)C=CC=CC=1>[CH3:20][O:21][C:22](=[O:33])[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:9][CH:7]([C:6]2[O:5][C:4]([C:10]3[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=3)=[N:3][C:2]=2[CH3:1])[CH3:8])=[CH:27][C:26]=1[CH3:32]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 13551833Methyl 3-(4-Hydroxy-2-methylphenyl)propanoateHCID 587657681-[4-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-yl]-ethanol

Product 1

HCID 693568003-(2-Methyl-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-yl]-ethoxy}-phenyl)-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1-[4-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-yl]-ethanol (0.15 g, 0.553 mmol) and 3-(4-Hydroxy-2-methyl-phenyl)-propionic acid methyl ester (0.12 g, 0.610 mmol) are stirred in 10 mL toluene at 0° C. under a nitrogen atmosphere. Tri-n-butylphosphine (0.21 mL, 0.83 mmol) is added followed by 1,1′-(Azodicarbonyl)dipiperidine (0.21 g, 0.83 mmol). The mixture is allowed to stir at room temperature for 20 hr. The resulting slurry is concentrated under reduced pressure. 50 mL of a 1:1 solution of ethyl acetate:hexanes is added, and the slurry is filtered. The resulting solution is concentrated and purified by silica gel chromatography eluting with a mixture of 8:2 hexanes:ethyl acetate yielding 3-(2-Methyl-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-yl]-ethoxy}-phenyl)-propionic acid methyl ester as a white solid, 0.176 g (71%). MS (M++1) 446.

Workup

  1. concentrationThe resulting slurry is concentrated under reduced pressure
  2. addition50 mL of a 1:1 solution of ethyl acetate:hexanes is added
  3. filtrationthe slurry is filtered
  4. concentrationThe resulting solution is concentrated
  5. custompurified by silica gel chromatography
  6. washeluting with a mixture of 8:2 hexanes

Sources & evidence

ORD record
ord-fc016213eeaf42c5abbcd214cfeb67fa
Source dataset
uspto-grants-2006_12
Patent number
US07153878B2

Reaction notes

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