3-Quinuclidinol, (+)- → HCID 58046620, compound

HRID 2362914Notes

Reaction equation

HRID 2362914 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.CO.ClCCl.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

6

Reactant 2

HCID 7364113-Quinuclidinol, (+)-HCID 66652324HCID 66652324, compound

Product 1

HCID 58046620HCID 58046620, compound

Reagents, catalysts & solvents 3

HCID 110612Titanium tetraisopropoxideCatalystHCID 1140TolueneSolventHCID 21226129Dichloromethane methanolSolvent

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 (0.2 g, 0.36 mmol) and (S)-3-quinuclidinol (0.184 g, 1.44 mmol) in toluene (2 mL), was added titanium(IV)-i-propoxide (0.105 mL, 0.36 mmol, d=0.97). After refluxing for 18 h, the reaction mixture was diluted with 5% methanol/dichloromethane, washed with water and brine. The organic phase was dried over MgSO4, filtered, concentrated and isolated by reverse phase HPLC to obtain the title compound as an acetate salt (0.08 g, 34%); 1H NMR (DMSO-d6): δ 1.32-1.36 (m, 1H), 1.51-1.54 (m, 4H), 1.79-1.84 (m, 3H), 1.99-2.01 (m, 1H), 2.35 (t, 2H, J=6.8 Hz), 2.52-2.72 (m, 11H), 3.15-3.21 (m, 1H), 3.85 (t, 2H, J=6.8 Hz), 4.61 (d, 4H, J=13.2 Hz), 4.90-4.92 (m, 1H), 6.76 (t, 1H, J=6.8 Hz), 6.84 (d, 2H, J=8 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. washwashed with water and brine
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customisolated by reverse phase HPLC

Sources & evidence

ORD record
ord-8cfaa34328534cc09abdf799ee52cdf2
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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