Potassium Phosphate, Tribasic → HCID 67409967、化合物

HRID 515216ノート

反応式

HRID 515216 の反応式
[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:26])=[O:25].Cl[C:29]1[CH:36]=[C:35]([OH:37])[CH:34]=[CH:33][C:30]=1[C:31]#[N:32].P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>O1CCOCC1.O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:29]3[CH:36]=[C:35]([OH:37])[CH:34]=[CH:33][C:30]=3[C:31]#[N:32])=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:25])=[O:26]

参加物

9

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 5927972-Chloro-4-hydroxybenzonitrileHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 67413064HCID 67413064、化合物

生成物 1

HCID 67409967HCID 67409967、化合物

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (12-1) (2.0 g, 5.0 mmol, 1 eq), 2-chloro-4-hydroxybenzonitrile (0.84 g, 5.5 mmol, 1.1 eq), tripotassium phosphate (2.1 g, 10.0 mmol, 2.0 eq), S-Phos (0.20 g, 0.5 mmol, 0.1 eq), and palladium(II) acetate (56 mg, 0.25 mmol, 0.05 eq) were combined in dioxane (20 mL) and water (3 mL). The resulting mixture was heated at 100° C. for 16 hours. The reaction mixture was allowed to cool to room temperature. The mixture was then diluted with EtOAc (100 mL), washed with water (20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (80 g SiO2, 0-80% EtOAc in hexanes) to afford 2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-hydroxybenzonitrile (12-2) as a white solid. LRMS m/z (M+H) 392.3 found, 392.1 required.

後処理

  1. temperatureto cool to room temperature
  2. washwashed with water (20 mL) and brine (20 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash chromatography (80 g SiO2, 0-80% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-77d9c800d13a42228e348ac7afb6a0b2
出典データセット
uspto-grants-2015_08
特許番号
US09108937B2

反応ノート

読み込み中…