Methanol → HCID 86597237, compound

HRID 1793456Notes

Reaction equation

HRID 1793456 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=O)[C:12](=O)[N:11]3[C@H:16]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=4)[CH2:17][CH2:18][C@H:10]3[CH2:9]2)=[CH:4][C:3]=1[O:29][CH3:30].B.C1COCC1.CO>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]3[C@H:16]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=4)[CH2:17][CH2:18][C@@H:10]3[CH2:9]2)=[CH:4][C:3]=1[O:29][CH3:30]

Participants

5

Reactant 3

HCID 887MethanolHCID 2723981Borane;tetrahydrofuranHCID 23395646HCID 23395646, compound

Product 1

HCID 86597237HCID 86597237, compoundYield 30.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(±)-cis-2-(4-Chloro-3-methoxy-phenyl)-6-(3,4-dimethoxy-phenyl)-hexahydro-pyrrolo[1,2-a]pyrazine-3,4-dione (49.7 mg, 0.115 mmol) was dissolved in dry THF (10 mL) and BH3.THF (1 mL, 1 mmol) was added dropwise to the mixture, which was then heated at reflux overnight. The solution was cooled to 0° C. and MeOH (2 mL) was added dropwise. The solvent was removed by evaporation and the crude product was dissolved in MeOH (10 mL) and 12N HCl (2 mL). The solution was refluxed for 4 hours. The reaction mixture was concentrated (˜2 mL) followed by basification with 1N NaOH. The aqueous solution was extracted with CH2Cl2 (3×25 mL). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The crude products were purified by preparatory TLC eluting with CH2Cl2/MeOH (97:3) to yield the (±)-cis-(20.3 mg, 43.8%) and (±)-trans-2-(4-chloro-3-methoxy-phenyl)-6-(3,4-dimethoxy-phenyl)-hexahydro-pyrrolo[1,2-a]pyrazine (14.3 mg, 30.9%) with (±)-cis-2-(4-chloro-3-methoxy-phenyl)-6-(3,4-dimethoxy-phenyl)-hexahydro-pyrrolo[1,2-a]pyrazine eluting further up the plate. (±)-trans-2-(4-Chloro-3-methoxy-phenyl)-6-(3,4-dimethoxy-phenyl)-hexahydro-pyrrolo[1,2-a]pyrazine 1H NMR (CDCl3) δ 7.20 (d, J=8.7 Hz, 1H, ArH), 6.89–6.83 (m, 3H, ArH), 6.47–6.40 (m, 2H, ArH), 4.16 (m, 1H), 3.95–3.84 (m, 1H), 3.90 (s, 3H, OCH3), 3.88 (s, 6H, OCH3), 3.58–3.46 (m, 1H), 3.41–3.36 (m, 1H), 3.26–3.22 (m, 1H), 2.99–2.71 (m, 3H), 2.34–2.20 (m, 2H), 1.95–1.83 (m, 1H), 1.64–1.54 (m, 1H). LCMS m/z 403 (M++1, 100, 1.90 min).

Workup

  1. temperaturewas then heated
  2. temperatureat reflux overnight
  3. customThe solvent was removed by evaporation
  4. dissolutionthe crude product was dissolved in MeOH (10 mL)
  5. temperatureThe solution was refluxed for 4 hours
  6. concentrationThe reaction mixture was concentrated (˜2 mL)
  7. extractionThe aqueous solution was extracted with CH2Cl2 (3×25 mL)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customThe crude products were purified by preparatory TLC
  12. washeluting with CH2Cl2/MeOH (97:3)

Sources & evidence

ORD record
ord-24de49017a5a42adad724ff1a71c63b1
Source dataset
uspto-grants-2006_07
Patent number
US07081458B2

Reaction notes

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