Hydrochloric Acid → Tert-butyl 5-(4-tert-butoxycarbonyl-3-methyl-phenyl)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrole-2-carboxylate

HRID 589645

Reaction equation

HRID 589645 reaction equation
[C:1]([O:5][C:6](=[O:52])[C:7]1[CH:12]=[CH:11][C:10]([C:13](=O)[CH2:14][C:15]([CH:28]([N:36]=C(C2C=CC=CC=2)C2C=CC=CC=2)[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=2)[C:16]([F:19])([F:18])[F:17])=[CH:9][C:8]=1[CH3:51])([CH3:4])([CH3:3])[CH3:2].Cl.O>CC(C)=O>[C:1]([O:5][C:6]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH2:14][C:15]([C:20]3[CH:21]=[C:22]([Cl:27])[CH:23]=[C:24]([Cl:26])[CH:25]=3)([C:16]([F:18])([F:17])[F:19])[CH:28]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[N:36]=2)=[CH:9][C:8]=1[CH3:51])=[O:52])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 866960024-[3-[(Benzhydrylidene-amino)-tert-butoxycarbonyl-methyl]-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester

Product 1

HCID 86696003Tert-butyl 5-(4-tert-butoxycarbonyl-3-methyl-phenyl)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrole-2-carboxylateYield 76.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Similarly, the reaction was carried out under similar conditions: To a solution of 4-[3-[(Benzhydrylidene-amino)-tert-butoxycarbonyl-methyl]-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester (426 mg, one diastereoisomer, obtained in example P12) in acetone (12 mL) was added hydrochloric acid (6 mL, 10%) and the solution was stirred at ambient temperature for 3 hours. Water was then added and the reaction mixture was extracted with ethylacetate and the combined organic fractions were dried over sodium sulfate. The crude product was purified by flash chromatography (0% to 05% dichloromethane in heptane) to afford tert-butyl 5-(4-tert-butoxycarbonyl-3-methyl-phenyl)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrole-2-carboxylate (248 mg) as a white solid. 19F NMR (376 MHz, CDCl3) δ −75.20 ppm (1 diastereoisomers). Chiral HPLC analysis (Chiralpack AS-RH, acetonitrile:water:methanol=55:5:40, 1 ml/min, retention time 22.87 minutes (minor enantiomer) and 25.52 minutes (major isomer) indicated that the reaction proceeded with little enantioselectivity.

Workup

  1. extractionthe reaction mixture was extracted with ethylacetate
  2. dry with materialthe combined organic fractions were dried over sodium sulfate
  3. customThe crude product was purified by flash chromatography (0% to 05% dichloromethane in heptane)

Sources & evidence

ORD record
ord-b8473c29f9d1423da78725445f0a03b4
Source dataset
uspto-grants-2016_01
Patent number
US09233920B2

Linked notes

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