Triphenylphosphine → 2-[4-(1-azabicyclo[2.2.2]oct-3-yloxy)phenyl]-1H-indole

HRID 1441401Notes

Reaction equation

HRID 1441401 reaction equation
[C:1]([C:3]1[CH:17]=[CH:16][C:6]([O:7][CH:8]2[CH:13]3[CH2:14][CH2:15][N:10]([CH2:11][CH2:12]3)[CH2:9]2)=[CH:5][CH:4]=1)#[CH:2].FC(F)(F)C([NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1I)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CCOC(C)=O.[Cu]I>[N:10]12[CH2:15][CH2:14][CH:13]([CH2:12][CH2:11]1)[CH:8]([O:7][C:6]1[CH:16]=[CH:17][C:3]([C:1]3[NH:22][C:23]4[C:28]([CH:2]=3)=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:4][CH:5]=1)[CH2:9]2

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 15346132,2,2-trifluoro-N-(2-iodophenyl)acetamideHCID 210726033-(4-Ethynylphenoxy)quinuclidine

Product 1

HCID 114839822-[4-(1-azabicyclo[2.2.2]oct-3-yloxy)phenyl]-1H-indole

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Under N2, the mixture of product from Example 6A (114 mg, 0.5 mmol), the product from Example 6B (157 mg, 0.5 mmol), CuI (Strem Chemicals, 14 mg, 0.075 mmol), PPh3 (Aldrich, 39 mg, 0.15 mmol) and K3PO4 (212 mg, 1 mmol) in dioxane (5 mL) was stirred at 80° C. for 20 h. After the reaction was complete, it was diluted with EtOAc (30 mL) and washed with brine (2×5 mL). The organic solution was concentrated under reduced pressure and the title compound was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.30) as solid (70 mg, yield, 44%). 1H NMR (300 MHz, CD3OD) δ 1.45-1.59 (m, 1H), 1.65-1.91 (m, 2H), 2.00-2.14 (m, 1H), 2.17-2.24 (m, 1H), 2.75-3.01 (m, 5H), 3.31-3.42 (m, 1H), 4.54-4.62 (m, 1H), 6.66 (d, J=0.7 Hz, 1H), 6.93-7.00 (m, 3H), 7.01-7.08 (m, 1H), 7.35 (dq, J=8.2, 1.0 Hz, 1H), 7.48 (dq, J=7.8, 0.7 Hz, 1H), 7.71 (dt, J=8.8, 2.6 Hz, 2H) ppm. MS (DCI/NH3): m/z 319 (M+H)+.

Workup

  1. washwashed with brine (2×5 mL)
  2. concentrationThe organic solution was concentrated under reduced pressure
  3. customthe title compound was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.30) as solid (70 mg, yield, 44%)

Sources & evidence

ORD record
ord-9ca8c3d5bb754684bc2544b1eecb7bf1
Source dataset
uspto-grants-2010_02
Patent number
US07655657B2

Reaction notes

Loading…