Dichloromethane → 1-Benzyl-4-(4-chloro-phenyl)-2,5-dihydro-1H-pyrrole-3-carboxylic acid

HRID 1880220Notes

Reaction equation

HRID 1880220 reaction equation
CO[CH2:3][N:4]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:5][Si](C)(C)C.F[C:18](F)(F)[C:19]([OH:21])=[O:20].[CH2:24]([Cl:26])Cl>>[CH2:10]([N:4]1[CH2:3][C:10]([C:11]2[CH:16]=[CH:15][C:24]([Cl:26])=[CH:13][CH:12]=2)=[C:18]([C:19]([OH:21])=[O:20])[CH2:5]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

4

Reactant 3

HCID 6344Dichloromethane2×HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amine

Product 1

HCID 593718091-Benzyl-4-(4-chloro-phenyl)-2,5-dihydro-1H-pyrrole-3-carboxylic acidYield 76%

Conditions

Temperature
25 °C

Procedure

A solution of N-(methoxymethyl)-N-(phenylmethyl)-N-(trimethylsilyl)methylamine (201.6 g, 849 mmol) in CH2Cl2 (600 mL) was added dropwise over a 30 minutes period to a stirred solution of 3-(4-chlorophenyl)-2-propionic acid ethyl ester (125.9 g, 566 mmol) and trifluoroacetic acid (4.3 mL, 114 mmol) in CH2Cl2 (400 mL) at 0° C. The ice bath was removed, and the solution was stirred at 25° C. for an additional 4 h. It was then concentrated and the reaction mixture was taken up in dioxane (1.2 L). Then 1N NaOH (146 mL) were added and the mixture was stirred at ambient temperature for 72 h. The volatiles were removed and the residue was extracted with TBDME and water. The organic phases were extracted with water and the combined aqueous phases were acidified with aqueous HCl (10%). Upon stirring at ambient temperature over night a precipitation formed which was isolated, washed with water and ethanol and dried under high vacuum to yield the title product (148 g, 76%) as a colorless solid. ES-MS m/e: 314.8 (M+H+).

Workup

  1. customThe ice bath was removed
  2. concentrationIt was then concentrated
  3. additionThen 1N NaOH (146 mL) were added
  4. stirringthe mixture was stirred at ambient temperature for 72 h
  5. customThe volatiles were removed
  6. extractionthe residue was extracted with TBDME and water
  7. extractionThe organic phases were extracted with water
  8. stirringUpon stirring at ambient temperature over night
  9. customa precipitation
  10. customformed which
  11. customwas isolated
  12. washwashed with water and ethanol
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-dba517e0ea6146cf9d0a9810664c0ee4
Source dataset
uspto-grants-2012_11
Patent number
US08318759B2

Reaction notes

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