Dimethyl Sulfoxide → 4-(1-(2-(Dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylic acid tert-butyl ester

HRID 1685194Notes

Reaction equation

HRID 1685194 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CS(C)=O.[OH-].[K+].Cl.Cl[CH2:38][CH2:39][N:40]([CH3:42])[CH3:41]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH2:38][CH2:39][N:40]([CH3:42])[CH3:41])[CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:27])([F:28])[F:29])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 679Dimethyl SulfoxideHCID 14797Potassium HydroxideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 178451792HCID 178451792, compound

Product 1

HCID 672648444-(1-(2-(Dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylic acid tert-butyl esterYield 95.6%

Conditions

Temperature
45 °C

Procedure

Combine a solution of 4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (25.00 g; 1.00 equiv; 60.47 mmol) in DMSO (200.00 mL; 2.82 mol) with KOH (powder) (9.98 g; 151.18 mmol) and heat the mixture to 45° C. To this solution, add 2-chloro-N,N-dimethylethanamine hydrochloride (10.45 g; 1.20 equiv; 72.57 mmol). Stir the mixture at 45° C. for 3 h. Pour the mixture into ice-water, stir at RT and extract with EA. Wash the organic layer with water (3×) and brine; dry over MgSO4, filter and concentrate in vacuo to give the title compound (28.00 g; 57.79 mmol; 95.56%) as a yellow oil and use without further purification. 1H NMR (300 MHz, DMSO): 8.04-8.00 (m, 2H), 7.74 (s, 1H), 7.46 (t, J=9.9 Hz, 1H), 4.06-3.99 (m, 4H), 3.03-2.93 (m, 3H), 2.57 (t, J=6.3 Hz, 2H), 2.19 (s, 6H), 1.81-1.77 (m, 2H), 1.70-1.55 (m, 2H), 1.42 (s, 9H).

Workup

  1. stirringstir at RT
  2. extractionextract with EA
  3. washWash the organic layer with water (3×) and brine
  4. dry with materialdry over MgSO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-2b753c1357384ca2830d7e172e229b47
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

Loading…