Hydrochloric Acid → 9-chloro-3-carbobenzyloxy-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]-quinoxalin-5(6H)-one

HRID 989043Notes

Reaction equation

HRID 989043 reaction equation
[C:1]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20](Cl)=[CH:19][C:18]=2[N+:24]([O-])=O)[CH:13]([C:27](O)=[O:28])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[ClH:30]>C(O)(=O)C.[Fe]>[Cl:30][C:21]1[CH:22]=[C:17]2[C:18]([NH:24][C:27](=[O:28])[CH:13]3[CH2:12][N:11]([C:1]([O:3][CH2:4][C:5]4[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=4)=[O:2])[CH2:16][CH2:15][N:14]32)=[CH:19][CH:20]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 180047874-Carbobenzyloxy-l-(4-chloro-2-nitrophenyl)piperazine-2-carboxylic acid

Product 1

HCID 121094739-chloro-3-carbobenzyloxy-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]-quinoxalin-5(6H)-oneYield 37%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of the above residue 4-carbobenzyloxy-l-(4-chloro-2-nitrophenyl)piperazine-2-carboxylic acid in 200 ml glacial acetic acid warmed to 60° C. was added iron powder (14 g) in portions. The reaction was heated at 60° C. for 3 h. The reaction was cooled to rt and 1N HCl was added. The resulting precipitate was filtered and dried. The crude material was dissolved in methylene chloride and passed through a plug of celite. The filtrate was concentrated to a dark red residue. This was purified by the Biotage 40i (4.0×15.0 cm column, load methylene chloride, elute 30-50% ethyl acetate/hexanes) to give 9-chloro-3-carbobenzyloxy-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]-quinoxalin-5(6H)-one as an off-white solid (4.8 g, 37% yield over 3 steps). 1H NMR (CDCl3, 300 MHz) δ7.32-7.37 (m, 5H), 6.82-6.85 (m, 1H), 6.68-6.75 (m, 2H), 5.18 (m, 2H), 4.73 (m, 1H), 4.31 (m, 1H), 3.49-3.54 (m, 2H), 3.07 (m, 2H), 2.74-2.81 (m, 1H) ppm. MS (ESI) m/z=372 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to rt
  2. filtrationThe resulting precipitate was filtered
  3. customdried
  4. dissolutionThe crude material was dissolved in methylene chloride
  5. concentrationThe filtrate was concentrated to a dark red residue
  6. customThis was purified by the Biotage 40i (4.0×15.0 cm column, load methylene chloride, elute 30-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4a7e21dccbbd4de98828652e1d5afe76
Source dataset
uspto-grants-2003_10
Patent number
US06638934B2

Reaction notes

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