Tributylphosphine → (1-Methyl-6-{2-[3-methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propoxy}-1H-indol-3-yl)-acetic acid methyl ester

HRID 490780Notes

Reaction equation

HRID 490780 reaction equation
[CH3:1][C:2]1[C:6]([CH:7]([CH3:10])[CH2:8][OH:9])=[CH:5][N:4]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[N:3]=1.C(P(CCCC)CCCC)CCC.[CH3:34][O:35][C:36](=[O:49])[CH2:37][C:38]1[C:46]2[C:41](=[CH:42][C:43](O)=[CH:44][CH:45]=2)[N:40]([CH3:48])[CH:39]=1>C1(C)C=CC=CC=1>[CH3:34][O:35][C:36](=[O:49])[CH2:37][C:38]1[C:46]2[C:41](=[CH:42][C:43]([O:9][CH2:8][CH:7]([C:6]3[C:2]([CH3:1])=[N:3][N:4]([C:11]4[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][CH:12]=4)[CH:5]=3)[CH3:10])=[CH:44][CH:45]=2)[N:40]([CH3:48])[CH:39]=1

Participants

5

Reactant 3

HCID 13831TributylphosphineHCID 57675473[6-hydroxy-1-methyl-1H-indole-3-yl]acetic acid methyl esterHCID 587338162-[3-Methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propan-1-ol

Product 1

HCID 69054260(1-Methyl-6-{2-[3-methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propoxy}-1H-indol-3-yl)-acetic acid methyl esterYield 58.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

2-[3-Methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propan-1-ol (150 mg, 0.5276 mmol) is dissolved into anhydrous toluene (2 mL) and cooled in an ice bath to 0° C. with stirring under nitrogen. Tributyl phosphine (200 uL, 0.7914 mmol) is added by syringe followed by 1-1′-azodicarbonyl-dipiperidine (200 mg, 0.7914 mmol). Finally, (6-Hydroxy-1-methyl-1H-indol-3-yl)-acetic acid methyl ester (145 mg, 0.6596 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 (1-Methyl-6-{2-[3-methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-propoxy}-1H-indol-3-yl)-acetic acid methyl ester (150 mg, 0.309 mmol) or 59%.

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-d40757ecb75747e48d99a5d1ee0bb396
Source dataset
uspto-grants-2009_05
Patent number
US07528160B2

Reaction notes

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