p-Toluenesulfonic acid → (2S,4S)-4-Fluoropyrrolidine-2-carbonitrile 4-methylbenzenesulfonate

HRID 1367109Notes

Reaction equation

HRID 1367109 reaction equation
[C:1]([C@@H:3]1[CH2:7][C@H:6]([F:8])[CH2:5][N:4]1C(OC(C)(C)C)=O)#[N:2].[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22]([OH:25])(=[O:24])=[O:23])=[CH:18][CH:17]=1>C(#N)C>[C:16]1([CH3:26])[CH:17]=[CH:18][C:19]([S:22]([OH:25])(=[O:23])=[O:24])=[CH:20][CH:21]=1.[C:1]([C@@H:3]1[CH2:7][C@H:6]([F:8])[CH2:5][NH:4]1)#[N:2]

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 18453438tert-Butyl (2S,4S)-2-cyano-4-fluoropyrrolidine-1-carboxylate

Product 1

HCID 72699082(2S,4S)-4-Fluoropyrrolidine-2-carbonitrile 4-methylbenzenesulfonate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of Step 1 intermediate (40 g, 186.72 mmol) in acetonitrile (400 ml) was added p-toluene sulfonic acid (64.3 g, 373.33 mmol) and the solution was stirred at for 24 h at room temperature under nitrogen atmosphere. The solvent was evaporated under reduced pressure to afford a brown residue, which was triturated with petroleum ether (100 ml) to give a filterable solid. The solid was collected by filtration and dried to give 45 g of the product as an off-white solid; 1H NMR (CDCl3, 300 MHz) δ 2.31 (s, 3H), 2.37-2.65 (m, 2H), 3.76-3.87 (m, 2H), 5.10 (br s, 2H), 5.33 (br d, J=51.6 Hz, 1H), 7.19 (d, J=8.1 Hz, 2H), 7.75 (d, J=8.1 Hz, 2H).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customto afford a brown residue, which
  3. customwas triturated with petroleum ether (100 ml)
  4. customto give a filterable solid
  5. filtrationThe solid was collected by filtration
  6. customdried

Sources & evidence

ORD record
ord-3923b64ac8844743908bdf029e2e4a43
Source dataset
uspto-grants-2011_02
Patent number
US07893103B2

Reaction notes

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