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

HRID 1799768Notes

Reaction equation

HRID 1799768 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.C([O:19][C:20](=[O:30])[C:21]#[C:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)C.FC(F)(F)C(O)=O.[OH-].[Na+]>C(Cl)Cl>[CH2:10]([N:4]1[CH2:3][C:22]([C:23]2[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=2)=[C:21]([C:20]([OH:30])=[O:19])[CH2:5]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 641307Ethyl 3-(4-chlorophenyl)propiolate

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

At r.t., a solution of N-(methoxymethyl)-N-(phenylmethyl)-N-(trimethylsilyl)methyl amine (116.8 g, 0.49 mol) in CH2Cl2 (260 ml) was added dropwise over 90 min to a stirred solution of (4-chloro-phenyl)-propynoic acid ethyl ester (72.0 g, 0.34 mol) and trifluoroacetic acid (2.5 ml, 0.03 mol) in CH2Cl2 (350 ml). The reaction mixture was stirred at 25° C. overnight and afterwards evaporated to dryness. The residue was dissolved in dioxane (0.8 l); an aqueous solution of NaOH (91.0 ml, 1.02 mol, 3 eq.) was added, and the resulting emulsion was stirred at r.t. for 48 h. The low boiling organic solvent was removed under vacuum, water (0.9 l) was added, and the aqueous layer was separated and washed with TBME (1 l). The aqueous layer was then acidified to a pH value of 2.5 by addition of 25% HCl. The resulting suspension was stirred overnight; the white precipitate was filtered off, washed with water and ethanol and dried under high vacuum to yield 62.0 g (60%) of IIa as a white solid.

Workup

  1. customafterwards evaporated to dryness
  2. dissolutionThe residue was dissolved in dioxane (0.8 l)
  3. stirringthe resulting emulsion was stirred at r.t. for 48 h
  4. customThe low boiling organic solvent was removed under vacuum, water (0.9 l)
  5. additionwas added
  6. customthe aqueous layer was separated
  7. washwashed with TBME (1 l)
  8. additionThe aqueous layer was then acidified to a pH value of 2.5 by addition of 25% HCl
  9. stirringThe resulting suspension was stirred overnight
  10. filtrationthe white precipitate was filtered off
  11. washwashed with water and ethanol
  12. customdried under high vacuum
  13. customto yield 62.0 g (60%) of IIa as a white solid

Sources & evidence

ORD record
ord-321136f371324687aa805138948d2144
Source dataset
uspto-grants-2013_01
Patent number
US08344161B2

Reaction notes

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