Sulfuric Acid → rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid

HRID 1807092Notes

Reaction equation

HRID 1807092 reaction equation
C([O:5][C:6]([CH:8]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=2[F:20])[C:11]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([F:30])[CH:24]=2)([C:21]#[N:22])[CH:10]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[NH:9]1)=[O:7])(C)(C)C.OS(O)(=O)=O>>[Cl:19][C:15]1[C:14]([F:20])=[C:13]([CH:12]2[C:11]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([F:30])[CH:24]=3)([C:21]#[N:22])[CH:10]([CH2:31][C:32]([CH3:34])([CH3:35])[CH3:33])[NH:9][CH:8]2[C:6]([OH:7])=[O:5])[CH:18]=[CH:17][CH:16]=1

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 67296858rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl ester

Product 1

HCID 67299695rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acidYield 98.1%

Conditions

Temperature
0 °C

Procedure

A mixture of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl ester (0.6 g, 1.15 mmol) was cooled to 0° C., then conc. H2SO4 (2 mL) was added slowly. The reaction was stirred at RT for 2 hours. The mixture was then poured into ice and extracted with EtOAc. The organic phase was separated, dried over Na2SO4, filtered and solvent was removed under reduced pressure to yield a residue that was triturated with ethyl acetate/heptane and the precipitates were collected by filtration and washed with ether to yield the product rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (0.526 g, 98.1%) as a white solid. HRMS (ES+) m/z Calcd for C23H22Cl2F2N2O2S+H [(M+H)+]: 467.1099. found: 467.1097.

Workup

  1. additionThe mixture was then poured into ice
  2. extractionextracted with EtOAc
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customsolvent was removed under reduced pressure
  7. customto yield a residue that
  8. customwas triturated with ethyl acetate/heptane
  9. filtrationthe precipitates were collected by filtration
  10. washwashed with ether

Sources & evidence

ORD record
ord-29ce4bb4459247a39abad50227f249fc
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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