3-Quinuclidinol, (-)- → HCID 58046619, compound

HRID 2362884Notes

Reaction equation

HRID 2362884 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[NH:17][C:16]3=[O:24])[CH2:8][CH2:7]2)[N:5]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:4][N:3]1[CH2:31][C:32]1[CH:33]=[C:34]([CH:39]=[CH:40][CH:41]=1)[C:35]([O:37][CH3:38])=[O:36].[N:42]12[CH2:49]C[CH:45]([CH2:46][CH2:47]1)[C@@H:44](O)[CH2:43]2>C1(C)C=CC=CC=1.CC(O)C.CC(O)C.CC(O)C.CC(O)C.[Ti]>[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[NH:17][C:16]3=[O:24])[CH2:8][CH2:7]2)[N:5]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:4][N:3]1[CH2:31][C:32]1[CH:33]=[C:34]([CH:39]=[CH:40][CH:41]=1)[C:35]([O:37][C@@H:38]1[CH:45]2[CH2:46][CH2:47][N:42]([CH2:43][CH2:44]2)[CH2:49]1)=[O:36]

Participants

5

Reactant 2

HCID 914043-Quinuclidinol, (-)-HCID 66652324HCID 66652324, compound

Product 1

HCID 58046619HCID 58046619, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 110612Titanium tetraisopropoxideCatalystHCID 1140TolueneSolvent

Procedure

To a refluxing solution of methyl 3-((4-oxo-8-(3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (0.33 g, 0.59 mmol) and (R)-3-quinuclidinol (0.3 g, 2.4 mmol) in toluene (5 mL), was added titanium(IV)-i-propoxide (0.173 mL, 0.59 mmol, d=0.97). After refluxing for 18 h, the reaction mixture was concentrated in vacuo and isolated by reverse phase HPLC to obtain the title compound (0.13 g, 34%); 1H NMR (DMSO-d6): δ 1.31-1.34 (m, 1H), 1.51-1.55 (m, 4H), 1.78-1.88 (m, 3H), 1.98-2.01 (m, 1H), 2.33 (t, 2H, J=7.2 Hz), 2.52-2.72 (m, 11H), 3.15-3.21 (m, 1H), 3.85 (t, 2H, J=6.8 Hz), 4.59-4.62 (m, 4H), 4.90-4.92 (m, 1H), 6.76 (t, 1H, J=7.2 Hz), 6.84 (d, 2H, J=8.4 Hz), 6.96 (d, 3H, J=2.4 Hz), 7.17-7.24 (m, 3H), 7.52-7.59 (m, 2H), 7.87-7.92 (m, 2H), 10.80 (br, 1H); MS for C38H44N6O4 m/z 649.11(M+H)+.

Workup

  1. temperatureAfter refluxing for 18 h
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customisolated by reverse phase HPLC

Sources & evidence

ORD record
ord-63207656e22e4858947578c488203d89
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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