Hydrochloric Acid → (R)-3-(3-ethoxycarbonyl-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester

HRID 1269521Notes

Reaction equation

HRID 1269521 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([C:7]2[CH:8]=[CH:9][C:10]([CH3:18])=[C:11]([CH:17]=2)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:2]1.C(O)(=O)[C@H]([C@@H](C(O)=O)O)O.[F:29][C:30]([F:47])([F:46])[C:31]1[CH:45]=[CH:44][C:34]([CH2:35][O:36][C:37](N2C=CN=C2)=[O:38])=[CH:33][CH:32]=1.Cl>C(OCC)(=O)C.O>[F:29][C:30]([F:46])([F:47])[C:31]1[CH:45]=[CH:44][C:34]([CH2:35][O:36][C:37]([N:1]2[CH2:6][CH2:5][CH2:4][C@H:3]([C:7]3[CH:8]=[CH:9][C:10]([CH3:18])=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:17]=3)[CH2:2]2)=[O:38])=[CH:33][CH:32]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 68882567Imidazole-1-carboxylic acid 4-trifluoromethylbenzyl esterHCID 86593890(R)-Ethyl 5-(3-piperidinyl)-2-methylbenzoate D-tartaric acid

Product 1

HCID 68885831(R)-3-(3-ethoxycarbonyl-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

(R)-Ethyl 5-(3-piperidinyl)-2-methylbenzoate-D-tartaric acid (2.02 g, 5.08 mmol) was dissolved in 100 mL ethyl acetate and washed with 100 mL saturated aqueous NaHCO3. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The resultant oil was taken up in 10 mL toluene and imidazole-1-carboxylic acid 4-trifluoromethyl-benzyl ester (1.37 g, 5.08 mmol) was added. The reaction was stirred for 72 h at room temperature under nitrogen. The reaction was diluted with water (200 mL), acidified with 1N aqueous hydrochloric acid and extracted with diethyl ether (2×150 mL). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 10% ethyl acetate/hexanes to yield 2.12 g (93%) of the desired (R)-3-(3-ethoxycarbonyl-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester as a clear oil.

Workup

  1. washwashed with 100 mL saturated aqueous NaHCO3
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. extractionextracted with diethyl ether (2×150 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customchromatographed with 10% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-e97901b2ea954c30a4a7540ed788c376
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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