Hydrochloric Acid → 4-[(R)-4-(3,5-dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid tert-butyl ester

HRID 589631Notes

Reaction equation

HRID 589631 reaction equation
[C:1]([O:5][C:6](=[O:34])[C:7]1[CH:12]=[CH:11][C:10]([C:13](=O)[CH2:14][C@@:15]([C:24]2[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)([CH2:20][N+:21]([O-])=O)[C:16]([F:19])([F:18])[F:17])=[CH:9][C:8]=1[CH3:33])([CH3:4])([CH3:3])[CH3:2].Cl>CN(C)C=O.[Zn]>[C:1]([O:5][C:6](=[O:34])[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH2:14][C@:15]([C:24]3[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=3)([C:16]([F:19])([F:18])[F:17])[CH2:20][N:21]=2)=[CH:9][C:8]=1[CH3:33])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 547615654-[(R)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester

Product 1

HCID 547617404-[(R)-4-(3,5-dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid tert-butyl esterYield 29%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

To a vigorously stirred suspension of zinc (0.060 g, 0.913 mmol) in dimethylformamide (2.0 ml) was added a solution of 4-[(R)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester (0.190 g, 0.365 mmol) in dimethylformamide (2.0 ml). The resulting mixture was warmed to 80° C. and 37% aqueous hydrochloric acid (3.0 ml) was added very slowly to minimize the foaming. After stirring for 2 hours the reaction was cooled to room temperature and quenched by adding a pH 7 buffer solution. The mixture was extracted with dichloromethane; the organic layer was washed with water (3×) and brine. The crude product was purified by flash chromatography (6% ethyl acetate in cyclohexane) to afford 4-[(R)-4-(3,5-dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid tert-butyl ester as a pale yellow oil (0.050 g, 29%).

Workup

  1. temperaturewas cooled to room temperature
  2. customquenched
  3. additionby adding a pH 7 buffer solution
  4. extractionThe mixture was extracted with dichloromethane
  5. washthe organic layer was washed with water (3×) and brine
  6. customThe crude product was purified by flash chromatography (6% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-b3dd9f70ae9f4f9fbdc74c747d68686d
Source dataset
uspto-grants-2016_01
Patent number
US09233920B2

Reaction notes

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