Hydrochloric Acid → 3-[3-(1-Ethoxycarbonyl-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl ester

HRID 1269511Notes

Reaction equation

HRID 1269511 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[C:5]([CH3:20])([O:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]2[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]2)[CH:9]=1)[CH3:6])[CH3:2].[CH:22]([C:25]1[CH:39]=[CH:38][C:28]([CH2:29][O:30][C:31](N2C=CN=C2)=[O:32])=[CH:27][CH:26]=1)([CH3:24])[CH3:23].Cl>C1(C)C=CC=CC=1.O>[CH:22]([C:25]1[CH:39]=[CH:38][C:28]([CH2:29][O:30][C:31]([N:16]2[CH2:17][CH2:18][CH2:19][CH:14]([C:10]3[CH:11]=[CH:12][CH:13]=[C:8]([O:7][C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:21])([CH3:20])[CH3:6])[CH:9]=3)[CH2:15]2)=[O:32])=[CH:27][CH:26]=1)([CH3:24])[CH3:23]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 18448505Imidazole-1-carboxylic acid-(4-isopropyl)benzyl esterHCID 688830642-Methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid ethyl ester

Product 1

HCID 688828523-[3-(1-Ethoxycarbonyl-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl esterYield 77.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid ethyl ester (Preparation 2; Method D; 7.60 g, 17.21 mmol) in 20 mL toluene was added imidazole-1-carboxylic acid-(4-isopropyl)benzyl ester (4.20 g, 17.21 mmol) and stirred for 18 h at ambient temperature. The reaction was diluted with water (300 mL), acidified with 1 N HCl and extracted with diethyl ether (2×200 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 6.23 g (77%) of 3-[3-(1-ethoxycarbonyl-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl ester as a clear oil.

Workup

  1. extractionextracted with diethyl ether (2×200 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customchromatographed with 10% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-58b1ef02df314b5282c7c65bbf088c61
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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