Triethylamine → 4-Cyclobutyl-3-(4-cyclohexyloxy-phenyl)-2-hydroxy-4-oxo-butyric acid ethyl ester

HRID 2168716Notes

Reaction equation

HRID 2168716 reaction equation
[CH:1]1([C:5](=[O:20])[CH2:6][C:7]2[CH:12]=[CH:11][C:10]([O:13][CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)=[CH:9][CH:8]=2)[CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[C:28]([O:32][CH2:33][CH3:34])(=[O:31])[CH:29]=[O:30]>C1COCC1>[CH2:33]([O:32][C:28](=[O:31])[CH:29]([OH:30])[CH:6]([C:7]1[CH:8]=[CH:9][C:10]([O:13][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]2)=[CH:11][CH:12]=1)[C:5]([CH:1]1[CH2:2][CH2:3][CH2:4]1)=[O:20])[CH3:34]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 70211Ethyl oxoacetateHCID 673757531-Cyclobutyl-2-(4-cyclohexyloxy-phenyl)-ethanone

Product 1

HCID 673730064-Cyclobutyl-3-(4-cyclohexyloxy-phenyl)-2-hydroxy-4-oxo-butyric acid ethyl esterYield 31.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-cyclobutyl-2-(4-cyclohexyloxy-phenyl)-ethanone (3.60 mmol, 0.98 g) and triethylamine (3.60 mmol, 0.51 mL) in THF (2.0 mL) was added a solution of ethyl glyoxylate (50% in toluene, 18.0 mmol, 3.82 mL) and continued stirring for 12 h at room temperature. After removal of volatiles under reduced pressure, the crude product was pre-absorbed onto 10 g SiO2 followed by purification on a 24 g SiO2 cartridge using a 0-30% ethyl acetate/hexanes gradient to give 4-cyclobutyl-3-(4-cyclohexyloxy-phenyl)-2-hydroxy-4-oxo-butyric acid ethyl ester (0.42 g).

Workup

  1. customAfter removal of volatiles under reduced pressure
  2. customthe crude product was pre-absorbed onto 10 g SiO2
  3. customfollowed by purification on a 24 g SiO2 cartridge

Sources & evidence

ORD record
ord-9616058beb1e425c96d41bb10b272623
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

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