(7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol → (7R,8aS)-2-benzyl-7-[(5-cyclopropylpyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazine

HRID 240427Notes

Reaction equation

HRID 240427 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[CH2:14][C@H:15]([OH:17])[CH2:16][C@H:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].Br[C:25]1[CH:30]=[N:29][C:28]([CH:31]2[CH2:33][CH2:32]2)=[CH:27][N:26]=1>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[CH2:14][C@H:15]([O:17][C:25]3[CH:30]=[N:29][C:28]([CH:31]4[CH2:33][CH2:32]4)=[CH:27][N:26]=3)[CH2:16][C@H:10]2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 14914621(7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-olHCID 23665647Potassium tert-butoxideHCID 457876352-Bromo-5-cyclopropylpyrazine

Product 1

HCID 86680439(7R,8aS)-2-benzyl-7-[(5-cyclopropylpyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To (7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 19D, 2.323 g, 10 mmol) in tetrahydrofuran (60 mL) at room temperature was added potassium tert-butoxide (14 mL, 1 M in tetrahydrofuran). After 10 minutes, 2-bromo-5-cyclopropylpyrazine (2.249 g, 11.3 mmol) in tetrahydrofuran (3 mL) was added. The mixture was stirred at room temperature for 2 days. The mixture was concentrated and diluted with dichloromethane (200 mL). This solution was washed with water (30 mL), dried over sodium sulfate, and filtered. The organic phase was concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol=15:1) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.80 (m, 2H), 0.92 (m, 2H), 1.78 (m, 3H), 2.08-2.38 (m, 5H), 2.70 (m, 1H), 2.83 (m, 2H), 3.53 (m, 3H), 5.24 (m, 1H), 7.28 (m, 5H), 8.12 (m, 2H); MS (ESI) m/z 351 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with dichloromethane (200 mL)
  3. washThis solution was washed with water (30 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationThe organic phase was concentrated
  7. customThe residue was purified by chromatography on silica gel (dichloromethane/methanol=15:1)

Sources & evidence

ORD record
ord-5a7a048735f14ba980e8235b7b7caaa8
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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