Diisopropylamine → HCID 9884652, 화합물

HRID 494863노트

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HRID 494863 반응식
[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

참가 물질

9

반응물 4

HCID 7912DiisopropylamineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 11175139HCID 11175139, 화합물HCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidine

생성물 1

HCID 9884652HCID 9884652, 화합물수율 30%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매

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온도
45 °C

실험 절차

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).]

후처리

  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

출처 및 근거

ORD 기록
ord-549d4f3a4a8f45b5a83e8e50c0766457
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07538138B2

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