Trifluoroacetic acid → HCID 86617385, compound

HRID 1435149Notes

Reaction equation

HRID 1435149 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:31]=[C:32]([Cl:34])[CH:33]=1)[CH2:12][N:13]([CH2:18][C@@H:19]1[CH2:23][CH2:22][CH2:21][N:20]1C(OC(C)(C)C)=O)[CH2:14][CH:15]([CH3:17])[CH3:16].[C:35]([OH:44])(=[O:43])[C@@H:36]([C@H:38]([C:40]([OH:42])=[O:41])[OH:39])[OH:37].C1CCCCC1>ClCCl>[C:40]([C@@H:38]([C@H:36]([C:35]([OH:44])=[O:43])[OH:37])[OH:39])([OH:42])=[O:41].[CH3:16][CH:15]([CH3:17])[CH2:14][N:13]([CH2:18][C@@H:19]1[CH2:23][CH2:22][CH2:21][NH:20]1)[CH2:12][C:11]1[CH:10]=[C:9]([Cl:8])[CH:33]=[C:32]([Cl:34])[CH:31]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 8078CyclohexaneHCID 444305L-Tartaric acidHCID 86617384HCID 86617384, compound

Product 1

HCID 86617385HCID 86617385, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1.5 ml, 15 mol, 10 eq) is added to a solution of tert-butyl (2S)-2-{[(3,5-dichlorobenzyl)(isobutyl)amino]methyl}pyrrolidine-1-carboxylate (0.611 g, 1.5 mmol, 1 eq) in dichloromethane (5 ml). After 16 hours if not complete by LCMS add an additional portion of trifluoroacetic acid (1.5 ml, 15 mol, 10 eq). After 72 hrs the solvent is removed in vacuo, methanol is added to the residue and the solution is loaded onto a SCX-2 (5 g) column. The column is washed with methanol (10 ml) and then the basic material is eluted with 2M ammonia in methanol (10 ml) and the solvent is removed in vacuo. The residue is dissolved in isopropanol (5 ml) and L-tartaric acid (1 eq) is added. The solution is heated to dissolve, then cooled and is left to stand in a fridge for 2 hrs, if no crystals have formed cyclohexane is added and the surface is scratched with a glass rod. The solid formed is filtered and dried in a vacuum oven at 60° C. for 16 hrs to give the N-(2-methylpropyl)-N-{[3,5-dichlorophenyl]-methyl}-(2S)-pyrrolidine-2-yl-methylamine L-Tartrate (0.23 g, 33%). 1H NMR (300 MHz, CD3OH) δH: 7.26 (3H, s) 4.29 (2H, s, tartrate) 3.44-3.78 (3H, m) 3.06-3.30 (4H, m) 2.42-2.71 (2H, m) 2.00-2.19 (3H, m) 1.83-1.99 (2H, m) 1.65-1.81 (1H, m) 1.46-1.64 (1H, m) 0.79 (6H, dd, J=6.5 and 3.2), LCMS: Rt=3.52 (12 min method) [M+H]=315.4.

Workup

  1. customAfter 72 hrs the solvent is removed in vacuo, methanol
  2. additionis added to the residue
  3. washThe column is washed with methanol (10 ml)
  4. washthe basic material is eluted with 2M ammonia in methanol (10 ml)
  5. customthe solvent is removed in vacuo
  6. dissolutionThe residue is dissolved in isopropanol (5 ml)
  7. temperatureThe solution is heated
  8. dissolutionto dissolve
  9. temperaturecooled
  10. waitis left
  11. additionis added
  12. customThe solid formed
  13. filtrationis filtered
  14. customdried in a vacuum oven at 60° C. for 16 hrs

Sources & evidence

ORD record
ord-ab452f5538f44acea38e59bef823b796
Source dataset
uspto-grants-2009_11
Patent number
US07615648B2

Reaction notes

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