1-(Prop-2-yn-1-yl)pyrrolidine → (3-fluoro-4-(3-(pyrrolidin-1-yl)prop-1-ynyl)phenyl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone

HRID 626176Notes

Reaction equation

HRID 626176 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)=[CH:12][CH:11]=2)=[O:9])=[CH:4][C:3]=1[F:23].[CH2:24]([N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1)[C:25]#[CH:26]>C(N(CC)CC)C>[F:23][C:3]1[CH:4]=[C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)=[CH:12][CH:11]=2)=[O:9])[CH:6]=[CH:7][C:2]=1[C:26]#[C:25][CH2:24][N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

4

Reactant 2

HCID 2996161-(Prop-2-yn-1-yl)pyrrolidineHCID 89672898(4-bromo-3-fluorophenyl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone

Product 1

HCID 89672877(3-fluoro-4-(3-(pyrrolidin-1-yl)prop-1-ynyl)phenyl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanoneYield 36.4%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

A 100 mL Schlenk flask was charged with (4-bromo-3-fluorophenyl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone (1.10 g, 2.90 mmol), tetrakis(tri-phenylphosphine)Palladium(0) (0.34 g, 0.29 mmol, 10 mol %), cuprous iodide (0.11 g, 0.58 mmol, 20 mol %), triethylamine (20 mL), and 1-(prop-2-ynyl)pyrrolidine (0.63 g, 5.80 mmol), and the flask was flushed with nitrogen three times. The mixture was stirred at 80° C. for 2 h. The solvent was evaporated under vacuum and the residue was purified by column chromatography to afford the desired product as a yellow solid (0.43 g, 36.4% yield).

Workup

  1. customthe flask was flushed with nitrogen three times
  2. customThe solvent was evaporated under vacuum
  3. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-d9a63f1d75674601a90a8a4c55922a2f
Source dataset
uspto-grants-2016_04
Patent number
US09309211B2

Reaction notes

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