Triphenylphosphine → 2-(1-Azabicyclo[2.2.2]octan-3-yloxy)-9H-carbazole

HRID 553040Notes

Reaction equation

HRID 553040 reaction equation
[OH:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[NH:5][C:4]=2[CH:3]=1.[N:15]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[CH:17](O)[CH2:16]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.ClCCl>[N:15]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[CH:17]([O:1][C:2]1[CH:14]=[CH:13][C:12]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[NH:5][C:4]=3[CH:3]=1)[CH2:16]2

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 15381(+-)-3-QuinuclidinolHCID 935512-HydroxycarbazoleHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 113008232-(1-Azabicyclo[2.2.2]octan-3-yloxy)-9H-carbazoleYield 59.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. mixture of 2-hydroxy-9H-carbazole (369 mg, 2.02 mmol; Aldrich), quinuclidin-3-ol (260 mg, 2.05 mmol; Aldrich), and triphenylphosphine (646 mg, 2.47 mmol; Aldrich) in THF (10 mL) was added diethylazodicarboxylate (320 μL, 2.03 mmol; Lancaster). After 1 h, the reaction mixture was allowed to warm to room temperature and was stirred for 3 d. The mixture was diluted with dichloromethane, washed with saturated aq. NaHCO3, dried over MgSO4, and purified by flash chromatography (80 g silica gel, eluting with 1-16% of 10% NH4OH/MeOH in CH2Cl2) to afford the title compound as an oil (350 mg, 1.20 mmol, 59% yield). Trituration of the oil with ethyl acetate produced a solid. 1H NMR (300 MHz, methanol-d4) δ 7.92 (1H, d, J=6 Hz), 7.90 (1H, d, J=8 Hz), 7.37 (1H, d, J=8 Hz), 7.26 (1H, ddd, J=7, 7, 1 Hz), 7.10 (1H, ddd, J=8, 8, 1 Hz), 6.92 (1H, d, J=2 Hz), 6.78 (1H, dd, J=8, 2 Hz), 4.59 (1H, m), 3.36 (1H, ddd, J=14, 8, 2 Hz), 3.04-2.75 (5H, m), 2.22 (1H, m), 2.11 (1H, m), 1.88-1.65 (2H, m), 1.51 (1H, m). MS (DCI/NH3): m/z 293 (M+1)+. Anal. Calcd. for C19H20N2O.0.1C4H8O2: C, 77.36; H, 6.96; N, 9.30. Found: C, 77.04; H, 7.23; N, 9.45.

Workup

  1. washwashed with saturated aq. NaHCO3
  2. dry with materialdried over MgSO4
  3. custompurified by flash chromatography (80 g silica gel, eluting with 1-16% of 10% NH4OH/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-6c3c61700fb040d2ae46f3fc9b6d436c
Source dataset
uspto-grants-2011_05
Patent number
US07951791B2

Reaction notes

Loading…