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

HRID 1799770Notes

Reaction equation

HRID 1799770 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:31])[C:21]#[C:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[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:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=2)=[C:21]([C:20]([OH:31])=[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 67233873(3,4-Dichloro-phenyl)-propynoic acid ethyl ester

Product 1

HCID 593718131-Benzyl-4-(3,4-dichloro-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 (262.5 g, 1.06 mol) in CH2Cl2 (0.6 l) was added dropwise over 60 min to a solution of (3,4-dichloro-phenyl)-propynoic acid ethyl ester (172.0 g, 0.71 mol) and trifluoroacetic acid (5.4 ml, 0.07 mol) in CH2Cl2 (0.7 l). The reaction mixture was stirred at 25° C. for 2 h. The reaction mixture was then evaporated to dryness, and the residue was dissolved in dioxane (1.6 l). An aqueous solution of NaOH (1.0 l, 1.9 mol, 2.8 eq.) was added. The resulting emulsion was stirred at r.t. for 20 h, and the low boiling organic solvent was removed under vacuum. Water (2.0 l) was added, and the aqueous layer was separated and washed with TBME (2 times 1.2 l). The aqueous layer was then acidified to a pH value of 2.5 by addition of 25% HCl. The resulting suspension was then stirred overnight, and the white precipitate was filtered off, washed with water and ethanol and dried under high vacuum to yield 205.0 g (83%) of IIb as a white solid.

Workup

  1. customThe reaction mixture was then evaporated to dryness
  2. dissolutionthe residue was dissolved in dioxane (1.6 l)
  3. stirringThe resulting emulsion was stirred at r.t. for 20 h
  4. customthe low boiling organic solvent was removed under vacuum
  5. additionWater (2.0 l) was added
  6. customthe aqueous layer was separated
  7. washwashed with TBME (2 times 1.2 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 then stirred overnight
  10. filtrationthe white precipitate was filtered off
  11. washwashed with water and ethanol
  12. customdried under high vacuum
  13. customto yield 205.0 g (83%) of IIb as a white solid

Sources & evidence

ORD record
ord-81e7325df8c44e35ae7e76c4c0879c3d
Source dataset
uspto-grants-2013_01
Patent number
US08344161B2

Reaction notes

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