Trifluoroacetic acid → HCID 86617380, compound

HRID 1435141Notes

Reaction equation

HRID 1435141 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][N:10]([CH2:17][C@H:18]1[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19]1)[CH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.FC(F)(F)C(O)=O.[C:37]([OH:46])(=[O:45])[C@@H:38]([C@H:40]([C:42]([OH:44])=[O:43])[OH:41])[OH:39]>ClCCl.C(O)(C)C>[C:42]([C@@H:40]([C@H:38]([C:37]([OH:46])=[O:45])[OH:39])[OH:41])([OH:44])=[O:43].[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][N:10]([CH2:17][C@H:18]1[CH2:22][CH2:21][NH:20][CH2:19]1)[CH:11]1[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 444305L-Tartaric acidHCID 69000456HCID 69000456, compound

Product 1

HCID 86617380HCID 86617380, compound

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (3R)-N-{[2,4-dichlorophenyl]methyl}-N-(tetrahydro-2H-pyran-4-yl)-1-tert-butyloxycarbonylpyrrolidine-3-yl-methylamine (0.36 g, 0.81 mmol) in dichloromethane (10 ml) is stirred at room temperature with trifluoroacetic acid (0.93 g, 8.10 mmol) overnight. The reaction mixture is concentrated in vacuo and the oil is dissolved in methanol, purified using a SCX-2 column (10 g), then washed with methanol. The basic product elutes with methanolic ammonia (2M). Evaporation to an oil and further purification by preparative LC-MS gives a colourless oil. Dissolve the oil in isopropyl alcohol and add L-tartaric acid (1 eq) then heat to give a clear solution. Crystallise by cooling to give the title compound as a colourless solid. 1H NMR (300 MHz, DMSO) δH: 7.57-7.56 (2H, m), 7.44-7.40 (1H, m), 3.88-3.85 (4H, m), 3.70 (2H, s), 3.24-3.03 (5H, m), 2.77-2.70 (1H, m), 2.59-2.51 (2H, m), 2.44-2.31 (1H, m), 1.94-1.88 (1H, m), 1.66-1.48 (6H, m), LCMS: Rt=4.22 (12 min method) [M+H]=343/5.

Workup

  1. concentrationThe reaction mixture is concentrated in vacuo
  2. dissolutionthe oil is dissolved in methanol
  3. custompurified
  4. washwashed with methanol
  5. customEvaporation
  6. customto an oil and further purification by preparative LC-MS
  7. customgives a colourless oil
  8. temperaturethen heat
  9. customto give a clear solution
  10. customCrystallise
  11. temperatureby cooling

Sources & evidence

ORD record
ord-bfe8cda559ea4256854f407e140eeb3d
Source dataset
uspto-grants-2009_11
Patent number
US07615648B2

Reaction notes

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