Trifluoroacetic acid → 3-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)benzonitrile

HRID 513015Notes

Reaction equation

HRID 513015 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C@H:10]2[CH2:14][C@H:13]([F:15])[CH2:12][N:11]2C(OC(C)(C)C)=O)[CH:6]=[C:7]([F:9])[CH:8]=1)#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:9][C:7]1[CH:8]=[C:3]([CH:4]=[C:5]([C@H:10]2[CH2:14][C@H:13]([F:15])[CH2:12][NH:11]2)[CH:6]=1)[C:1]#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66684286(2R,4S)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-fluoropyrrolidine-1-carboxylate

Product 1

HCID 666849673-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2R,4S)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-fluoropyrrolidine-1-carboxylate (I-14) (0.6 g, 1.95 mmol) in DCM (2 mL) at room temperature was added TFA (2 mL). The mixture was stirred at room temperature for 2 hours. All the solvents were removed under reduced pressure. The crude was diluted with EtOAc, washed with aqueous NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated to yield 3-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)benzonitrile (I-15). 1H NMR (400 MHz, CDCl3) δ 7.52 (s, 1 H), 7.43-7.37 (m, 1 H), 7.24-7.20 (m, 1 H), 5.28 (dt, J=3.6, 53.6 Hz, 1 H), 4.57 (dd, J=6.4, 9.6 Hz, 1 H), 3.44-3.18 (m, 2 H), 2.63-2.50 (m, 1 H), 1.72 (dddd, J=4.4, 10.0, 14.4, 39.6 Hz, 1H). MS m/z 209.1 (M+1)+.

Workup

  1. customAll the solvents were removed under reduced pressure
  2. additionThe crude was diluted with EtOAc
  3. washwashed with aqueous NaHCO3 and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ecb8edc9bbe446c2a22351df2990d8b3
Source dataset
uspto-grants-2015_08
Patent number
US09102671B2

Reaction notes

Loading…