Trifluoroacetic acid → (R)-3-(4,4-difluoropyrrolidin-2-yl)-5-fluorobenzonitrile

HRID 513018Notes

Reaction equation

HRID 513018 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C@H:10]2[CH2:14][C:13]([F:16])([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:16][C:13]1([F:15])[CH2:12][NH:11][C@@H:10]([C:5]2[CH:4]=[C:3]([CH:8]=[C:7]([F:9])[CH:6]=2)[C:1]#[N:2])[CH2:14]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68282459(R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4,4-difluoropyrrolidine-1-carboxylate

Product 1

HCID 66691400(R)-3-(4,4-difluoropyrrolidin-2-yl)-5-fluorobenzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4,4-difluoropyrrolidine-1-carboxylate (I-23) (0.45 g, 1.4 mmol) in DCM (3 mL) was added TFA (3 mL) and stirred at room temperature for 1 hour. 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 (R)-3-(4,4-difluoropyrrolidin-2-yl)-5-fluorobenzonitrile (I-24) as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.52 (s, 1 H), 7.42 (d, J=9.2 Hz, 1 H), 7.29-7.26 (m, 1 H), 4.46 (t, J=8.8 Hz, 1 H), 3.52-3.30 (m, 2 H), 2.74-2.60 (m, 1 H), 2.20-2.04 (m, 1 H), 1.90 (bs, 1 H). MS m/z 227.1 (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-29ba9566c63f4ef09c64e0854924043a
Source dataset
uspto-grants-2015_08
Patent number
US09102671B2

Reaction notes

Loading…