Potassium Iodide → (R)-N-(2-(3-(3-methoxyphenyl)-3-(2-methylphenyl)-2-propen-1-yloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester

HRID 1614820Notes

Reaction equation

HRID 1614820 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH3:22])=[CH:10][CH2:11][O:12][CH2:13][CH2:14]O)[CH:6]=[CH:7][CH:8]=1.C([Li])CCC.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[NH:39]1[CH2:44][CH2:43][CH2:42][C@@H:41]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:40]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C1(C)C=CC=CC=1.CC(C)=O>[CH2:48]([O:47][C:45]([C@@H:41]1[CH2:42][CH2:43][CH2:44][N:39]([CH2:14][CH2:13][O:12][CH2:11][CH:10]=[C:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH3:22])[CH2:40]1)=[O:46])[CH3:49]

Participants

9

Reactant 6

HCID 4875Potassium IodideHCID 73974-Toluenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 185582ethyl (3R)-piperidine-3-carboxylateHCID 536756102-(3-(3-Methoxyphenyl)-3-(2-methylphenyl)-2-propen-1-yloxy)ethanolHCID 178418339Butyllithium

Product 1

HCID 54033474(R)-N-(2-(3-(3-methoxyphenyl)-3-(2-methylphenyl)-2-propen-1-yloxy)ethyl)-3-piperidinecarboxylic acid ethyl esterYield 68%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 1140TolueneSolvent2×

Procedure

A solution of 2-(3-(3-methoxyphenyl)-3-(2-methylphenyl)-2-propen-1-yloxy)ethanol (7.6 g, 25.4 mmol) in dry toluene (150 ml) was cooled on an ice-bath and a solution of n-butyllithium in hexanes (11.2 ml, 2.5 M) was added dropwise. The reaction mixture was stirred for 0.5 h at room temperature and p-toluenesulphonyl chloride (5.3 g, 28 mmol) was added. The mixture was stirred at room temperature for 1.5 h. Ethyl (R)-3-piperidinecarboxylate (8.8 g, 50 mmol) and potassium carbonate (7.7 g, 50 mmol) were added and the mixture was stirred at room temperature for 4 h. Toluene (100 ml), acetone (50 ml) and potassium iodide (1.7 g) were added and the reaction mixture was heated at 75° C. for 84 h. The cooled reaction mixture was filtered and the solvent evaporated in vacuo. The residue was submitted to flash chromatography on silica gel (250 g) using a mixture of n-heptane and ethyl acetate (4:1) as eluent to give 7.5 g (68%) of (R)-N-(2-(3-(3-methoxyphenyl)-3-(2-methylphenyl)-2-propen-1-yloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil. TLC: rf=0.20 (SiO2 ; ethyl acetate).

Workup

  1. stirringThe mixture was stirred at room temperature for 1.5 h
  2. stirringthe mixture was stirred at room temperature for 4 h
  3. temperaturethe reaction mixture was heated at 75° C. for 84 h
  4. customThe cooled reaction mixture
  5. filtrationwas filtered
  6. customthe solvent evaporated in vacuo
  7. additiona mixture of n-heptane and ethyl acetate (4:1) as eluent

Sources & evidence

ORD record
ord-100ca098dc5044e6bfb9228299dd24ed
Source dataset
uspto-grants-1993_03
Patent number
US05198451

Reaction notes

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