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 490775ノート

反応式

HRID 490775 の反応式
[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

参加物

5

反応物 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

生成物 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 ester収率 58.6%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
0 °C

実験手順

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%.

後処理

  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

出典と根拠

ORDレコード
ord-c8d015c991514b8fa09f7074d21d5b66
出典データセット
uspto-grants-2009_05
特許番号
US07528160B2

反応ノート

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