Hydrochloric Acid → (+/-)-trans-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,8,8a,9,10,11,11a-octahydro-4H-pyrido[3,2,1-ij]pyrrolo[3,4-c]quinoline, bis-hydrochloride salt

HRID 1836564Notes

Reaction equation

HRID 1836564 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]3[C:16]4=[C:17]([CH2:19][CH2:20][CH2:21][N:15]4[CH2:14][C@@H:13]4[CH2:22][N:23](C(OC(C)(C)C)=O)[CH2:24][C@@H:12]34)[CH:18]=2)=[C:5]([C:32]([F:35])([F:34])[F:33])[CH:4]=1.FC(F)(F)C(O)=O.CCOCC.[ClH:48]>C(Cl)Cl.C(O)C>[ClH:48].[ClH:48].[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]3[C:16]4=[C:17]([CH2:19][CH2:20][CH2:21][N:15]4[CH2:14][C@@H:13]4[CH2:22][NH:23][CH2:24][C@@H:12]34)[CH:18]=2)=[C:5]([C:32]([F:35])([F:33])[F:34])[CH:4]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl Ether2×HCID 6422Trifluoroacetic acidHCID 23518425(+/-)-trans-tert-butyl 2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,8a,9,11,11a-hexahydro-4H-pyrido[3,2,1-ij]pyrrolo[3,4-c]quinoline-10(8H)-carboxylate

Product 1

HCID 131724531(+/-)-trans-2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,8,8a,9,10,11,11a-octahydro-4H-pyrido[3,2,1-ij]pyrrolo[3,4-c]quinoline, bis-hydrochloride saltYield 57%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (±)-trans-tert-butyl 2-[4-methoxy-2-(trifluoromethyl)phenyl]-5,6,8a,9,11,11a-hexahydro-4H-pyrido[3,2,1-ij]pyrrolo[3,4-c]quinoline-10(8H)-carboxylate (160 mg, 0.33 mmol) in 5 mL of methylene chloride was added 1 mL of trifluoroacetic acid. The mixture was allowed to stir at ambient temperature for 2 h and then was concentrated in vacuo. The residue was purified by preparative HPLC (C18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA). Product-containing fractions were combined, concentrated and partitioned between chloroform and saturated aqueous sodium carbonate. The organics were washed with brine, dried (K2CO3) and concentrated in vacuo. The residue (30 mg, 0.077 mmol) was dissolved in ethanol and ether and there was added 2M HCl in ether (0.077 mL, 0.15 mmol). The solvent was decanted and the remaining solid was triturated twice with ether and was dried in vacuo to afford 20 mg (57%) of the title compound of EXAMPLE 7 as an off white powder. 1H NMR (d6-dmso): δ 9.40 (broad s, 2H), 7.29-7.18 (m, 3H), 6.71 (s, 1H), 6.58 (s, 1H), 3.82 (s, 3H), 3.57-3.49 (m, 1H), 3.40-3.18 (m, 5H), 2.93-2.80 (m, 3H), 2.70-2.62 (m, 2H), 2.16-2.06 (m, 1H), 1.95-1.88 (m, 1H), 1.85-1.78 (m, 1H). LRMS (ES)+: 389.2 (M+H)+.

Workup

  1. concentrationwas concentrated in vacuo
  2. customThe residue was purified by preparative HPLC (
  3. washC18 reverse phase column, elution with a H2O/CH3CN gradient with 0.5% TFA)
  4. concentrationconcentrated
  5. custompartitioned between chloroform and saturated aqueous sodium carbonate
  6. washThe organics were washed with brine
  7. dry with materialdried (K2CO3)
  8. concentrationconcentrated in vacuo
  9. customThe solvent was decanted
  10. customthe remaining solid was triturated twice with ether
  11. customwas dried in vacuo

Sources & evidence

ORD record
ord-0abf9a9f9bec4df9a53672ead970a5e8
Source dataset
uspto-grants-2004_08
Patent number
US06777406B2

Reaction notes

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