Ethanol → (R)-3-(4-chlorophenyl)-1-(phenylmethyl)hexahydropyrazine dihydrochloride

HRID 2390918Notes

Reaction equation

HRID 2390918 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][N:12]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:11][CH2:10][N:9]2CC=C)=[CH:4][CH:3]=1.C(O)C>[Rh](Cl)(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[ClH:1].[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]2[NH:9][CH2:10][CH2:11][N:12]([CH2:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:13]2)=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 702EthanolHCID 68577181(R)-2-(4-chlorophenyl)-4-(phenylmethyl)-1-(2-propenyl)hexahydropyrazine

Product 1

HCID 68578904(R)-3-(4-chlorophenyl)-1-(phenylmethyl)hexahydropyrazine dihydrochlorideYield 101.6%

Reagents, catalysts & solvents 2

HCID 157991709Trichlororhodium;tris(triphenylphosphane)CatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To (R)-2-(4-chlorophenyl)-4-(phenylmethyl)-1-(2-propenyl)hexahydropyrazine (357 mg, 1.1 mmol) produced in Example 15, ethanol (3 mL), distilled water (0.2 mL) and tris(triphenylphosphine) rhodium chloride (30 mg, 0.05 equivalent) were added. The mixture was stirred at 95° C. for 18 hours, and was concentrated. To the concentrate, 1 N hydrochloric acid (5 mL) and toluene (5 mL) were added; and formed insolubles were removed by filtration. After the organic layer and aqueous layer was separated, the obtained aqueous layer (yield: 63%, chemical purity: 77.5 area %, optical purity: 97.7% e.e.) was concentrated. To the concentrate, acetone (10 mL) was added to precipitate crystals. The mixture was stirred at 25° C. for 1 hour, then cooled to 5° C., and further stirred for 1 hour. The crystals were separated by filtration under reduced pressure, then washed with acetone (5 mL), and dried under vacuum, to obtain 134 mg of the title compound as white crystals (yield: 44%, chemical purity: 99.1 area %, optical purity: 99.9% e.e.). The retention time in the chemical purity analysis method was 3.1 min.

Workup

  1. additionwere added
  2. concentrationwas concentrated
  3. additionTo the concentrate, 1 N hydrochloric acid (5 mL) and toluene (5 mL) were added
  4. customand formed insolubles
  5. customwere removed by filtration
  6. customAfter the organic layer and aqueous layer was separated
  7. concentrationthe obtained aqueous layer (yield: 63%, chemical purity: 77.5 area %, optical purity: 97.7% e.e.) was concentrated
  8. additionTo the concentrate, acetone (10 mL) was added
  9. customto precipitate crystals
  10. stirringThe mixture was stirred at 25° C. for 1 hour
  11. temperaturecooled to 5° C.
  12. stirringfurther stirred for 1 hour
  13. customThe crystals were separated by filtration under reduced pressure
  14. washwashed with acetone (5 mL)
  15. customdried under vacuum

Sources & evidence

ORD record
ord-4cbb795222b944a3a5b1267a2ac956ae
Source dataset
uspto-grants-2012_09
Patent number
US08273883B2

Reaction notes

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