Hydrochloric Acid → 3-(3-Cyano-phenyl)-2-pyrrolidin-2-ylidene-propionic acid methyl ester

HRID 901333Notes

Reaction equation

HRID 901333 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:12])[CH:6]=[C:7]1[CH2:11][CH2:10][CH2:9][NH:8]1.[C:13]([C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH2:18]Br)#[N:14].Cl>C1(C)C=CC=CC=1>[CH3:3][O:4][C:5](=[O:12])[C:6](=[C:7]1[CH2:11][CH2:10][CH2:9][NH:8]1)[CH2:18][C:17]1[CH:20]=[CH:21][CH:22]=[C:15]([C:13]#[N:14])[CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 97249Benzonitrile, 3-(bromomethyl)-HCID 69255134Methyl 2-pyrrolidin-2-ylideneacetate

Product 1

HCID 692550583-(3-Cyano-phenyl)-2-pyrrolidin-2-ylidene-propionic acid methyl esterYield 55.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a flask containing a 60% dispersion of NaH (0.91 g, 22.7 mmol), and toluene (60 mL), under nitrogen, is added Pyrrolidin-2-ylidene-acetic acid methyl ester (3.2 g, 22.7 mmol) and the mixture is refluxed for 1 h. The reaction mixture was cooled to 0° C. and a solution of m-cyanobenzylbromide (4.45 g, 22.7 mmol) in toluene (60 mL) is added dropwise. The reaction is allowed to warm to RT and then heated at 60° C. overnight. The mixture is cooled to RT and with vigorous stirring 1 N HCl is added to obtain a pH of 6. The toluene was decanted and dried over Na2SO4 and concentrated. Purification by flash chromatography (9:9:1 of CH2Cl2:hexanes:EtOAc) gave the title compound as a wet solid (3.2 g, 12.5 mmol). 1H NMR (CDCl3, 300 MHz) 8.32(br. s, 1H), 7.48-7.25(m, 4H), 3.63(s, 3H), 3.62-3.55(m, 2H), 3.53(s, 2H), 2.66-2.48(m, 2H), 2.10-1.90(m, 2H).

Workup

  1. temperaturethe mixture is refluxed for 1 h
  2. temperatureto warm to RT
  3. temperatureheated at 60° C. overnight
  4. temperatureThe mixture is cooled to RT
  5. additionis added
  6. customto obtain a pH of 6
  7. customThe toluene was decanted
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customPurification by flash chromatography (9:9:1 of CH2Cl2:hexanes:EtOAc)

Sources & evidence

ORD record
ord-971e019fcd564182a5510a06a7733751
Source dataset
uspto-grants-2008_04
Patent number
US07361663B2

Reaction notes

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