Sodium Iodide → (9aR)-benzyl 8-allyl-7-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate

HRID 2175794Notes

Reaction equation

HRID 2175794 reaction equation
O[C@@H:2]([C:22]1[C:23]([CH3:32])=[C:24]2[C:28](=[CH:29][CH:30]=1)[C:27](=[O:31])[O:26][CH2:25]2)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:6][C@H:5]1[CH2:20]O.S(Cl)(Cl)=O.[CH2:37]([NH2:40])[CH:38]=[CH2:39].[I-].[Na+]>C(OCC)(=O)C>[CH2:37]([N:40]1[CH:2]([C:22]2[C:23]([CH3:32])=[C:24]3[C:28](=[CH:29][CH:30]=2)[C:27](=[O:31])[O:26][CH2:25]3)[CH2:3][N:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[O:11])[CH2:6][C@H:5]2[CH2:20]1)[CH:38]=[CH2:39]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 7853AllylamineHCID 24386Thionyl ChlorideHCID 86727038HCID 86727038, compound

Product 1

HCID 86727039(9aR)-benzyl 8-allyl-7-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (S)-benzyl 4-((S)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-(hydroxymethyl)piperazine-1-carboxylate (1.4 g, 3.2 mmol) in thionyl chloride (20 mL, 274 mmol) was heated at reflux for 1 h. After removing the volatiles, the residue was dissolved in N,N-dimethylformamide (20 mL) and treated with allylamine (1.31 mL, 17.48 mmol) at 0° C. The resulting solution was treated with sodium iodide (0.088 g, 0.318 mmol) and heated at 90° C. for 1 h. The solution was diluted in ethyl acetate (300 mL) and was washed with saturated sodium bicarbonate three times, dried over sodium sulfate, concentrated and the residue was purified by MPLC on a Biotage system using 40-100% ethyl acetate/hexane to give the title compound. LC/MS: (M+1)+: 462.12.

Workup

  1. temperatureat reflux for 1 h
  2. customAfter removing the volatiles
  3. dissolutionthe residue was dissolved in N,N-dimethylformamide (20 mL)
  4. washwas washed with saturated sodium bicarbonate three times
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customthe residue was purified by MPLC on a Biotage system

Sources & evidence

ORD record
ord-55f56d2bf9ec418680489a4788f7996d
Source dataset
uspto-grants-2015_06
Patent number
US09062070B2

Reaction notes

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