Diisopropylamine → HCID 9884652、化合物

HRID 494863ノート

反応式

HRID 494863 の反応式
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14](=[O:16])[CH3:15])[CH:9]=2)=[CH:4][C:3]=1I.C1(P(C2CCCCC2)C2CCCCC2)C(C2C=CC=CC=2)=CC=CC=1.C(NC(C)C)(C)C.[CH2:50]([N:54]1[CH2:58][CH2:57][CH2:56][C@H:55]1[CH3:59])[CH2:51][C:52]#[CH:53]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Cu]I.CN(C)C=O.CC#N>[CH3:59][C@@H:55]1[CH2:56][CH2:57][CH2:58][N:54]1[CH2:50][CH2:51][C:52]1[O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:9]=[C:10]([C:14](=[O:16])[CH3:15])[CH:11]=[CH:12][CH:13]=3)=[CH:4][C:3]=2[CH:53]=1

参加物

9

反応物 4

HCID 7912DiisopropylamineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 11175139HCID 11175139、化合物HCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidine

生成物 1

HCID 9884652HCID 9884652、化合物収率 30%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
45 °C

実験手順

The product from Example 136B (1.15 g, 3.40 mmol), palladium (II) acetate (38 mg, 0.17 mmol), biphen-2-yl-dicyclohexylphosphine (119 mg, 0.34 mmol), diisopropylamine (4.8 mL, 34 mmol), and copper(I) iodide (76 mg, 0.40 mmol) were suspended in a 0.09 M MeCN solution of (R)-1-but-3-ynyl-2-methylpyrrolidine (45 mL, 4.0 mmol). N,N-dimethylformamide (10 mL) was added, and the mixture was heated at 45° C. overnight, cooled to room temperature, partitioned between CH2Cl2 (100 mL) and 5% aqueous ammonia (100 mL), worked up as usual but with 5% aqueous ammonia, filtered, and concentrated. The residue was dissolved into CH2Cl2 and washed consecutively with water and brine, dried (Na2SO4), concentrated, and chromatographed through silica with a gradient of 0 to 4% MeOH/CH2Cl2. The appropriate fractions were combined and rechromatographed with 50% CH2Cl2/hexanes followed by a gradient of 0 to 4% MeOH/CH2Cl2 to provide the title compound as a dark brown gum (30% yield). MS (APCI) m/z 348 (M+H)+; 1HNMR (300 MHz, CD3OD) δ 1.17 (d, 3H), 1.38-1.52 (m, 1H), 1.73-1.86 (m, 2H), 1.94-2.07 (m, 1H), 2.23-2.34 (m, 1H), 2.40-2.58 (m, 2H), 2.67 (s, 3H), 2.95-3.14 (m, 2H), 3.19-3.32 (m, 2H), 6.62 (s, 1H), 7.49-7.52 (m, 2H), 7.57 (dd, 1H), 7.78 (dd, 1H), 7.88 (ddd, 1H), 7.96 (ddd, 1H), 8.22 (dd, 1H).]

後処理

  1. temperaturecooled to room temperature
  2. custompartitioned between CH2Cl2 (100 mL) and 5% aqueous ammonia (100 mL)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved into CH2Cl2
  6. washwashed consecutively with water and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customchromatographed through silica with a gradient of 0 to 4% MeOH/CH2Cl2
  10. customrechromatographed with 50% CH2Cl2/hexanes

出典と根拠

ORDレコード
ord-549d4f3a4a8f45b5a83e8e50c0766457
出典データセット
uspto-grants-2009_05
特許番号
US07538138B2

反応ノート

読み込み中…