(7R,8aS)-2-benzyl-7-hydroxyhexahydropyrrolo[1,2-a]pyrazine-1,4-dione → (7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol

HRID 240425Notes

Reaction equation

HRID 240425 reaction equation
[CH2:1]([N:8]1[CH2:13][C:12](=O)[N:11]2[CH2:15][C@H:16]([OH:18])[CH2:17][C@H:10]2[C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[CH2:15][C@H:16]([OH:18])[CH2:17][C@H:10]2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 14914605(7R,8aS)-2-benzyl-7-hydroxyhexahydropyrrolo[1,2-a]pyrazine-1,4-dioneHCID 21226445Aluminium lithium hydride

Product 1

HCID 14914621(7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a suspension of Example 19C (60 g, 0.23 mol, 1 equivalent) in tetrahydrofuran (900 mL), lithium aluminum hydride (2 M in tetrahydrofuran, 460 mL, 0.92 mol, 4 equivalents) was added slowly at about 15° C. Then, the mixture was stirred at about 65° C. for 78 hours. The reaction mixture was cooled to 0-5° C., quenched using ethyl acetate (300 mL), water (60 mL), 10% NaOH solution (60 mL), followed by water (60 mL), and the mixture was stirred at 20-25° C. for 30 minutes. The suspension was filtered through diatomaceous earth, and the filtrate was concentrated. This crude material was purified by column chromatography on silica gel using a gradient of 0-10% methanol-ethyl acetate to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.46-1.49 (m, 2H), 1.68, (t, 1H, J=9.9 Hz), 1.91 (dd, 1H, J=5.4 Hz, J=8.9 Hz), 2.04-2.13 (m, 1H), 2.15-2.49 (m, 2H), 2.67 (d, 1H, J=10.3 Hz), 2.78 (d, 2H, J=5.4 Hz), 3.25 (dd, 1H, J=4.5 Hz, J=8.9 Hz), 3.47 (dd, 2H, J=4.5 Hz, J=17.4 Hz), 4.15-4.22 (m, 1H), 4.73 (bs, 1H), 7.23-7.318 (m, 5H); 13C NMR (75 MHz, DMSO-d6) δ ppm 39.74, 51.34, 52.64, 57.61, 60.72, 62.56, 63.16, 68.46, 127.26, 128.54, 129.2, 138.84; MS (ESI) m/z 233 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to 0-5° C.
  2. customquenched
  3. stirringthe mixture was stirred at 20-25° C. for 30 minutes
  4. filtrationThe suspension was filtered through diatomaceous earth
  5. concentrationthe filtrate was concentrated
  6. customThis crude material was purified by column chromatography on silica gel using a gradient of 0-10% methanol-ethyl acetate

Sources & evidence

ORD record
ord-af8f0f3f0e6f4c2b899384b1f58674bc
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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