Trifluoroacetic acid → Rac 4-{[(2r,3s,4r,5s)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-2-fluoro-benzoic acid

HRID 1807314Notes

Reaction equation

HRID 1807314 reaction equation
[Cl:1][C:2]1[C:3]([F:45])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:43]=[CH:42][C:34]([C:35]([O:37]C(C)(C)C)=[O:36])=[C:33]([F:44])[CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C@@:12]2([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@@H:9]([C:28]([NH:30][C:31]3[CH:43]=[CH:42][C:34]([C:35]([OH:37])=[O:36])=[C:33]([F:44])[CH:32]=3)=[O:29])[C@@H:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:45])=[C:16]([F:22])[CH:17]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 45137136tert-butyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-fluorobenzoate

Product 1

HCID 53358687Rac 4-{[(2r,3s,4r,5s)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-2-fluoro-benzoic acidYield 95.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 50 mL round-bottomed flask, tert-butyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-fluorobenzoate (170 mg, 257 μmol, Eq: 1.00) was combined with CH2Cl2 (3 mL) to give a colorless solution. TFA (3 ml) was added and the reaction was stirred for 6 hours. The crude reaction mixture was concentrated in vacuum, added DCM and concentrated again. Recrystallization from diethyl ether and hexanes afforded a white solid (148 mg, 93% yield). MS (ES+) m/z Calcd: [(M+H)+]: 604. found: 604.

Workup

  1. customto give a colorless solution
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuum
  4. additionadded DCM
  5. concentrationconcentrated again
  6. customRecrystallization from diethyl ether and hexanes

Sources & evidence

ORD record
ord-e82c92fd78eb40ab9890f04bd899124f
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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