Sodium hydride → HCID 67265095, compound

HRID 1685157Notes

Reaction equation

HRID 1685157 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].[H-].[Na+].[CH2:32]([O:39][C:40]([N:42]1[CH2:46][CH2:45][CH2:44][CH:43]1[CH2:47]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:41])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH2:47][CH:43]3[CH2:44][CH2:45][CH2:46][N:42]3[C:40]([O:39][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O: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 3

HCID 24758Sodium hydrideHCID 14821717HCID 14821717, compoundHCID 178451792HCID 178451792, compound

Product 1

HCID 67265095HCID 67265095, compoundYield 51.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

In a dry round bottom flask, charge 4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (1.5 g; 0.0036 mol; 1.0 equiv) in dry DMF (30 mL) and cool to 0° C. Add NaH (0.26 g; 0.011 mol; 3.0 equiv) in portions under nitrogen and stir at RT for 30 min. Add 2-(toluene-4-sulfonyloxymethyl)-pyrrolidine-1-carboxylic acid benzyl ester (2.46 g; 0.0072 mol; 2.0 equiv) at RT and heat at 40° C. overnight. Quench with cold water and extract in EA. Wash the organic layer with water and brine. Dry over anhydrous sodium sulfate and concentrate. Purify the crude residue on silica (100-200 mesh) with 10 to 20% EA/hexanes to give the title compound (1.14 g; 51.6%). (ES+): m/z=631 (M+H).

Workup

  1. customQuench with cold water
  2. extractionextract in EA
  3. washWash the organic layer with water and brine
  4. dry with materialDry over anhydrous sodium sulfate
  5. concentrationconcentrate
  6. customPurify the crude residue on silica (100-200 mesh) with 10 to 20% EA/hexanes

Sources & evidence

ORD record
ord-587a5bdf49e742fe8a551f6a03f58faf
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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