Tributylphosphine → 3-(4-(2-[4-Isopropyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-2-methyl-phenyl)-propionic acid methyl ester

HRID 860667Notes

Reaction equation

HRID 860667 reaction equation
[CH:1]([C:4]1[N:5]=[C:6]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[S:7][C:8]=1[CH:9]([CH3:12])[CH2:10][OH:11])([CH3:3])[CH3:2].C(P(CCCC)CCCC)CCC.[CH3:36][O:37][C:38](=[O:49])[CH2:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44](O)=[CH:43][C:42]=1[CH3:48]>C1(C)C=CC=CC=1>[CH3:36][O:37][C:38](=[O:49])[CH2:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44]([O:11][CH2:10][CH:9]([C:8]2[S:7][C:6]([C:13]3[CH:14]=[CH:15][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:17][CH:18]=3)=[N:5][C:4]=2[CH:1]([CH3:2])[CH3:3])[CH3:12])=[CH:43][C:42]=1[CH3:48]

Participants

5

Reactant 3

HCID 13831TributylphosphineHCID 13551833Methyl 3-(4-Hydroxy-2-methylphenyl)propanoateHCID 587657432-[4-Isopropyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propan-1-ol

Product 1

HCID 693589043-(4-(2-[4-Isopropyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-2-methyl-phenyl)-propionic acid methyl esterYield 47.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

2-[4-Isopropyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propan-1-ol (329 mg, 1.0 mmol) is dissolved into anhydrous toluene (5 mL) and cooled in an ice bath to 0° C. with stirring under nitrogen. Tributyl phosphine (400 uL, 1.50 mmol) is added by syringe followed by 1-1′-azodicarbonyl-dipiperidine (405 mg, 1.50 mmol). Finally, 3-(4-Hydroxy-2-methyl-phenyl)-propionic acid methyl ester (200 mg, 1.20 mmol) is then added. The reaction is allowed to stir under nitrogen at 0° C. for 1 hour, then room temperature and monitored by TLC and HPLC. Upon completion, the reaction is diluted with hexanes and allowed to stir vigorously for 10 min. The resulting white precipitate is then filtered away and the solution is concentrated under vacuum. The residue is further purified using either EtOAc/Hexanes (1:9) or Acetone/Hexanes (1:9) gradients on silica gel chromatography to yield 3-(4-{2-[4-Isopropyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-2-methyl-phenyl)-propionic acid methyl ester (239 mg, 0.4725 mmol) or 45%.

Workup

  1. stirringto stir under nitrogen at 0° C. for 1 hour
  2. customroom temperature
  3. stirringto stir vigorously for 10 min
  4. filtrationThe resulting white precipitate is then filtered away
  5. concentrationthe solution is concentrated under vacuum
  6. customThe residue is further purified

Sources & evidence

ORD record
ord-a98c1bde5a64492fb963e092d796e41d
Source dataset
uspto-grants-2006_12
Patent number
US07153878B2

Reaction notes

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