Sodium Bicarbonate → t-butyl[4-(9-hydroxy-2-methyl-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-acetate

HRID 1799042ノート

反応式

HRID 1799042 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][N:12]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:13]=2)O1.Cl[C:24]1[C:36]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:29]([C:38]([F:41])([F:40])[F:39])([OH:37])[C:28]=2[CH:27]=[C:26]([CH3:42])[CH:25]=1.C(=O)([O-])O.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:18]([O:17][C:15](=[O:16])[CH2:14][N:12]1[CH:13]=[C:9]([C:24]2[C:36]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:29]([OH:37])([C:38]([F:40])([F:41])[F:39])[C:28]=3[CH:27]=[C:26]([CH3:42])[CH:25]=2)[CH:10]=[N:11]1)([CH3:19])([CH3:20])[CH3:21]

参加物

8

反応物 4

HCID 516892Sodium BicarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 59216326tert-Butyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)acetateHCID 59492563(+)-4-chloro-2-methyl-9-trifluoromethyl-9H-fluoren-9-ol

生成物 1

HCID 59492691t-butyl[4-(9-hydroxy-2-methyl-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-acetate収率 59.8%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 22272177Toluene water溶媒

反応条件

温度
110 °C

実験手順

To a suspension of t-butyl [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-acetate (24.8 g), (+)-4-chloro-2-methyl-9-trifluoromethyl-9H-fluoren-9-ol (20.0 g), and sodium hydrogen carbonate (11.3 g) in toluene/water (200 ml/60 ml) were added palladium acetate (750 mg) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (2.75 g) at room temperature and the mixture was stirred at 110° C. for 2 hr. To the reaction mixture were added water (80 ml) and activated carbon (2.0 g) at room temperature and the mixture was stirred for 1 hr. The mixture was filtered through celite, and the solid was washed with tetrahydrofuran (100 ml). The filtrate was partitioned and the aqueous layer was extracted with ethyl acetate (100 ml). The combined organic layer was successively washed twice with water (100 ml) and once with saturated brine (100 ml), anhydrous sodium sulfate and silica gel (40 g) were added, and the mixture was stirred overnight. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was treated with n-hexane/ethyl acetate (2/1, 120 ml) solution, and the resulting slurry was filtered to give the title compound (17.8 g).

後処理

  1. stirringthe mixture was stirred for 1 hr
  2. filtrationThe mixture was filtered through celite
  3. washthe solid was washed with tetrahydrofuran (100 ml)
  4. customThe filtrate was partitioned
  5. extractionthe aqueous layer was extracted with ethyl acetate (100 ml)
  6. washThe combined organic layer was successively washed twice with water (100 ml) and once with saturated brine (100 ml), anhydrous sodium sulfate and silica gel (40 g)
  7. additionwere added
  8. stirringthe mixture was stirred overnight
  9. filtrationThe mixture was filtered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. additionThe obtained residue was treated with n-hexane/ethyl acetate (2/1, 120 ml) solution
  12. filtrationthe resulting slurry was filtered

出典と根拠

ORDレコード
ord-d8380874d8d549e4be48716c8245c418
出典データセット
uspto-grants-2013_01
特許番号
US08343994B2

反応ノート

読み込み中…