Methanol → 9-Chloro-3-carbobenzyloxy-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline

HRID 989044Notes

Reaction equation

HRID 989044 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([NH:6][C:7](=O)[CH:8]3[CH2:15][N:14]([C:16]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[O:17])[CH2:13][CH2:12][N:9]32)=[CH:4][CH:3]=1.B.C1COCC1.CO>C1COCC1>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([NH:6][CH2:7][CH:8]3[CH2:15][N:14]([C:16]([O:18][CH2:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)=[O:17])[CH2:13][CH2:12][N:9]32)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 2723981Borane;tetrahydrofuranHCID 121094739-chloro-3-carbobenzyloxy-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]-quinoxalin-5(6H)-one

Product 1

HCID 121094749-Chloro-3-carbobenzyloxy-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxalineYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 9-chloro-3-carbobenzyloxy-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a ]-quinoxalin-5(6H)-one (1.45 g, 3.9 mmol) in 50 ml THF was added a solution of borane-THF complex (1M in THF, 12.2 ml, 12.2 mmol). After 15 min, the reaction was heated to reflux. After MS showed the absence of starting material, the reaction mixture was cooled to rt. Methanol was added and the solution concentrated to a yellow residue. This was repeated and the crude material was purified by column chromatography using a Biotage© Flash 40i (4.0×15.0 cm column, load with methylene chloride, elute with 25-30% ethyl acetate/hexanes) to give 9-Chloro-3-carbobenzyloxy-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline as an off-white solid (898.3 mg, 65%). 1H NMR (CDCl3, 300 MHz) δ7.32-7.38 (m, 5H), 6.56-6.66 (m, 2H), 6.37-6.40 (m, 1H), 5.16 (s, 2H), 4.19 (m, 2H), 3.61-3.71 (m, 2H), 3.33-3.36 (m, 1H), 3.05-3.23 (m, 2H), 2.72-2.79 (m, 2H) ppm. MS (ESI) m/z=358 [M+H]+.

Workup

  1. temperaturethe reaction was heated to reflux
  2. concentrationthe solution concentrated to a yellow residue
  3. customthe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-f47ee08521574119944deeb07dbcdd24
Source dataset
uspto-grants-2003_10
Patent number
US06638934B2

Reaction notes

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