Imidazole-1-carboxylic acid 4-trifluoromethylbenzyl ester → 3-(3-Ethoxycarbonylmethoxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester

HRID 1269543Notes

Reaction equation

HRID 1269543 reaction equation
C(O)(=O)[C@@H]([C@H](C(O)=O)O)O.[CH2:11]([O:13][C:14](=[O:30])[CH2:15][O:16][C:17]1[CH:22]=[C:21]([CH:23]2[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]2)[CH:20]=[CH:19][C:18]=1[CH3:29])[CH3:12].[F:31][C:32]([F:49])([F:48])[C:33]1[CH:47]=[CH:46][C:36]([CH2:37][O:38][C:39](N2C=CN=C2)=[O:40])=[CH:35][CH:34]=1>C(OCC)(=O)C>[F:31][C:32]([F:48])([F:49])[C:33]1[CH:47]=[CH:46][C:36]([CH2:37][O:38][C:39]([N:25]2[CH2:26][CH2:27][CH2:28][CH:23]([C:21]3[CH:20]=[CH:19][C:18]([CH3:29])=[C:17]([O:16][CH2:15][C:14]([O:13][CH2:11][CH3:12])=[O:30])[CH:22]=3)[CH2:24]2)=[O:40])=[CH:35][CH:34]=1

Participants

4

Reactant 2

HCID 68882567Imidazole-1-carboxylic acid 4-trifluoromethylbenzyl esterHCID 68882790(2-Methyl-5-piperidin-3-yl-phenoxy)-acetic acid ethyl ester l-tartaric acid salt

Product 1

HCID 688836293-(3-Ethoxycarbonylmethoxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(2-methyl-5-piperidin-3-yl-phenoxy)-acetic acid ethyl ester L-tartaric acid salt (Example 12; 147 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 (93 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 118 mg (74%) of the desired 3-(3-ethoxycarbonylmethoxy-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-ecdcdc3824074e69b315effd2ecc0f0e
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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