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

HRID 1269506Notes

Reaction equation

HRID 1269506 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[C:11](N1C=CN=C1)(N1C=CN=C1)=[O:12].[CH2:23]([O:30][C:31](=[O:48])[C:32]([CH3:47])([O:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH:41]2[CH2:46][CH2:45][CH2:44][NH:43][CH2:42]2)[CH:36]=1)[CH3:33])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.Cl>C1(C)C=CC=CC=1.O>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]([N:43]2[CH2:44][CH2:45][CH2:46][CH:41]([C:37]3[CH:38]=[CH:39][CH:40]=[C:35]([O:34][C:32]([C:31]([O:30][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[O:48])([CH3:33])[CH3:47])[CH:36]=3)[CH2:42]2)=[O:12])=[CH:6][CH:5]=1)([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 74654-IsopropylphenolHCID 682631,1'-CarbonyldiimidazoleHCID 688839562-Methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester

Product 1

HCID 688829373-[3-(1-Benzyloxycarbonyl-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-phenyl esterYield 60.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

To a solution of 4-isopropylphenol (1.54 g, 11.32 mmol) in 10 mL toluene was added 1,1′-carbonyldiimidazole (1.84 g, 11.32 mmol). This solution was stirred 18 h at ambient temperature. 2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester (Preparation 2, Method C; 2.0 g, 5.66 mmol) was added in 5 mL toluene and the resultant solution was stirred 18 h at ambient temperature. 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 1.76 g (60%) of the desired 3-[3-(1-benzyloxycarbonyl-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-phenyl ester as a clear oil.

Workup

  1. extractionextracted with diethyl ether (2×150 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-63faad67bbcf4501bbbf3de6a2ab9157
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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