Water → 2-Tert-butoxycarbonyl-7-(methylthio)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole

HRID 392097Notes

Reaction equation

HRID 392097 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([O:24][C:25]([N:27]1[CH2:40][CH2:39][N:30]2[C:31]3[CH:32]=[C:33](I)[CH:34]=[CH:35][C:36]=3[CH2:37][CH:29]2[CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].[CH3:41][S:42][Sn](CCCC)(CCCC)CCCC.O>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:20]([O:24][C:25]([N:27]1[CH2:40][CH2:39][N:30]2[C:31]3[CH:32]=[C:33]([S:42][CH3:41])[CH:34]=[CH:35][C:36]=3[CH2:37][CH:29]2[CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 962WaterHCID 11776TriphenylphosphineHCID 11110497Methyl Tributylstannyl SulfideHCID 218687132-Tert-butoxycarbonyl-7-iodo-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole

Product 1

HCID 218687642-Tert-butoxycarbonyl-7-(methylthio)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoleYield 50%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

Triphenylphosphine (28 mg) was added in 1 portion to a stirred solution of palladium(II) acetate (6 mg) in THF (2.5 mL) at room temperate under Ar. After stirring at room temperature under Ar for 10 min a solution of 2-tert-butoxycarbonyl-7-iodo-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole (0.20 g, 0.5 mmol) in THF (5 mL) was added. The reaction was stirred at room temperature for 10 min then a solution of (methylthio)tributyltin (035 g, 1 mmol) in THF (2.5 mL) was added. The reaction was heated to reflux and stirred for 2 days. After allowing to cool to room temperature the mixture was poured into water (50 mL) and extracted. with ethyl acetate (3×30 mL). The combined organic extracts were washed with brine (r×50 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude oil. The oil was purified by flash column chromatography [SiO2; ethyl acetate-heptane (1:20)] to give the product as a yellow oil (0.08 g, 50%). NMR δH (400 MHz; CDCl3) 6.97 (1H, d, J 7.5 Hz), 6.56 (1H, dd, J 7.5, 1.5 Hz), 6.36 (1H, d, J 1l Hz), 3.94-4.26 (2H, m), 3.35-3.49 (2H, m), 2.78-2.96 (41, m), 2.49-2.55 (1H, m), 2.44 (311, s), 1.46 (9H, s).

Workup

  1. additionwas added
  2. temperatureThe reaction was heated
  3. temperatureto reflux
  4. stirringstirred for 2 days
  5. temperatureto cool to room temperature the mixture
  6. extractionextracted
  7. washThe combined organic extracts were washed with brine (r×50 mL)
  8. dry with materialdried (magnesium sulfate)
  9. filtrationfiltered
  10. customthe solvent removed under vacuum
  11. customto leave a crude oil
  12. customThe oil was purified by flash column chromatography [SiO2; ethyl acetate-heptane (1:20)]

Sources & evidence

ORD record
ord-8a7731882e07489b81cfddc663fb741f
Source dataset
uspto-grants-2004_10
Patent number
US06800627B1

Reaction notes

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