Trifluoroacetic acid → 6-(3-Aminopyrrolidin-1-yl)nicotinonitrile

HRID 252100Notes

Reaction equation

HRID 252100 reaction equation
FC(F)(F)C(O)=O.C(OC(=O)[NH:14][CH:15]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][N:21]=2)[CH2:16]1)(C)(C)C>ClCCl>[NH2:14][CH:15]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][N:21]=2)[CH2:16]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66854656tert-butyl N-[1-(5-cyanopyridin-2-yl)pyrrolidin-3-yl]carbamate

Product 1

HCID 210904066-(3-Aminopyrrolidin-1-yl)nicotinonitrileYield 101.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add trifluoroacetic acid (30 mL) to [1-(5-cyanopyridin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (7.95 g, 27.6 mmol) in dichloromethane (200 mL) and stir for 2 h. Concentrate, add toluene (100 mL) and reconcentrate to give a residue. Partition the residue between dichloromethane and an saturated aqueous solution of sodium bicarbonate and separate the layers. Extract the aqueous layer 5 times with 15:85 isopropyl alcohol:chloroform, combine the organic layers, dry (sodium sulfate), filter, and concentrate to give the title compound as a yellow oil (5.25 g). 1H NMR (400 MHz, CDCl3) δ 8.34 (d, 1H, J=2.5 Hz), 7.53-7.50 (m, 1H), 6.29 (d, 1H, J=8.8 Hz), 3.80-3.10 (m, 5H), 2.25-2.15 (m, 1H), 1.90-1.75 (m, 3H); MS (ES): m/z=189 [M+H]+.

Workup

  1. concentrationConcentrate
  2. additionadd toluene (100 mL)
  3. customto give a residue
  4. customPartition the residue between dichloromethane
  5. customan saturated aqueous solution of sodium bicarbonate and separate the layers
  6. extractionExtract the aqueous layer 5 times with 15:85 isopropyl alcohol
  7. dry with materialdry (sodium sulfate)
  8. filtrationfilter
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-30a3bd96318541cf8666735231ae7fc7
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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