Water → 4-methyl-1-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)-1H-imidazole

HRID 273082Notes

Reaction equation

HRID 273082 reaction equation
[CH3:1][C:2]1[N:3]=[C:4](S)[N:5]([CH2:7][C:8]2([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)=[CH:16][CH:15]=3)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:6]=1.O>C(O)C.[Ni]>[CH3:1][C:2]1[N:3]=[CH:4][N:5]([CH2:7][C:8]2([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)=[CH:16][CH:15]=3)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:6]=1

Participants

5

Reactant 2

HCID 962WaterHCID 178430224HCID 178430224, compound

Product 1

HCID 598375014-methyl-1-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)-1H-imidazoleYield 16%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Procedure

4-methyl-1-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)-1H-imidazole-2-thiol (0.6 g, 1.44 mmol) was dissolved in ethanol (20 mL), water (5 mL) was added, and the mixture was cooled in ice. Raney nickel (4 g) was added, the reaction mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was filtered though Arbocel® and concentrated in vacuo to provide a brown oil. This was purified by flash chromatography on silica gel eluting with ethyl acetate:diethylamine (95:5) to provide the title compound (0.086, 16%) as a clear oil. 1H NMR (400 MHz CDCl3) δ 1.80-1.90 (m, 6H), 2.08-2.18 (m, 7H), 2.65-2.80 (m, 6H), 3.50 (t, 2H), 3.80 (m, 2H), 3.90 (s, 2H), 4.05 (t, 2H), 6.10 (s, 1H), 6.70 (s, 1H), 6.89 (d, 2H), 7.0 (d, 2H). LRMS ESI+ m/z 384 [MH]+.

Workup

  1. temperaturethe mixture was cooled in ice
  2. filtrationThe reaction mixture was filtered though Arbocel®
  3. concentrationconcentrated in vacuo
  4. customto provide a brown oil
  5. customThis was purified by flash chromatography on silica gel eluting with ethyl acetate:diethylamine (95:5)

Sources & evidence

ORD record
ord-3157723bf48a4b02a834b61c487e1d6d
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

Loading…