Imidazole-1-carboxylic acid 4-trifluoromethylbenzyl ester → 3-[3-(1-Ethoxycarbonyl-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester

HRID 1269535Notes

Reaction equation

HRID 1269535 reaction equation
C(O)(=O)[C@@H]([C@H](C(O)=O)O)O.[CH2:11]([O:13][C:14](=[O:32])[C:15]([CH3:31])([O:17][C:18]1[CH:23]=[C:22]([CH:24]2[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]2)[CH:21]=[CH:20][C:19]=1[CH3:30])[CH3:16])[CH3:12].[F:33][C:34]([F:51])([F:50])[C:35]1[CH:49]=[CH:48][C:38]([CH2:39][O:40][C:41](N2C=CN=C2)=[O:42])=[CH:37][CH:36]=1>C(OCC)(=O)C>[F:33][C:34]([F:50])([F:51])[C:35]1[CH:49]=[CH:48][C:38]([CH2:39][O:40][C:41]([N:26]2[CH2:27][CH2:28][CH2:29][CH:24]([C:22]3[CH:21]=[CH:20][C:19]([CH3:30])=[C:18]([O:17][C:15]([C:14]([O:13][CH2:11][CH3:12])=[O:32])([CH3:31])[CH3:16])[CH:23]=3)[CH2:25]2)=[O:42])=[CH:37][CH:36]=1

Participants

4

Reactant 2

HCID 68882567Imidazole-1-carboxylic acid 4-trifluoromethylbenzyl esterHCID 688846382-Methyl-2-(2-methyl-5-piperidin-3-yl-phenoxy)-propionic acid ethyl ester l-tartaric acid salt

Product 1

HCID 688868503-[3-(1-Ethoxycarbonyl-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl esterYield 91%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2-methyl-2-(2-methyl-5-piperidin-3-yl-phenoxy)-propionic acid ethyl ester L-tartaric acid salt (Example 11; 155 mg, 0.34 mmol) was dissolved in 50 mL ethyl acetate and washed with 50 mL saturated aqueous NaHCO3. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The resultant oil was taken up in 3 mL toluene and imidazole-1-carboxylic acid 4-trifluoromethyl-benzyl ester (92 mg, 0.34 mmol) was added. The reaction was stirred for 18 h at room temperature under nitrogen. The reaction was flash chromatographed with 15% ethyl acetate/hexanes to yield 157 mg (91%) of the desired 3-[3-(1-ethoxycarbonyl-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester as a clear oil.

Workup

  1. washwashed with 50 mL saturated aqueous NaHCO3
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customchromatographed with 15% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-a4f4db91668049c393a02b347ba920f2
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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