Diisopropylamine → HCID 9884652, compound

HRID 494863Notes

Reaction equation

HRID 494863 reaction equation
[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

Participants

9

Reactant 4

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

Product 1

HCID 9884652HCID 9884652, compoundYield 30%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

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).]

Workup

  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

Sources & evidence

ORD record
ord-549d4f3a4a8f45b5a83e8e50c0766457
Source dataset
uspto-grants-2009_05
Patent number
US07538138B2

Reaction notes

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