Citric Acid → (5R,6RS)-6-((RS)-Acetoxy imidazo[1,2-a]quinoxalin-2-ylmethyl)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid p-Nitrobenzyl Ester

HRID 638846Notes

Reaction equation

HRID 638846 reaction equation
[CH:1]1[N:5]2[C:6]3[C:11]([N:12]=[CH:13][C:4]2=[N:3][C:2]=1[CH:14]=[O:15])=[CH:10][CH:9]=[CH:8][CH:7]=3.[Mg+2].[Br-].[Br-].[N+:19]([C:22]1[CH:40]=[CH:39][C:25]([CH2:26][O:27][C:28]([C:30]2[N:31]3[C@H:34]([S:35][CH:36]=2)[C@@H:33]([Br:37])[C:32]3=[O:38])=[O:29])=[CH:24][CH:23]=1)([O-:21])=[O:20].CNC1(NC)C=CN=CC1.[C:51](OC(=O)C)(=[O:53])[CH3:52].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(N(CC)CC)C.C1COCC1.C(#N)C>[N+:19]([C:22]1[CH:40]=[CH:39][C:25]([CH2:26][O:27][C:28]([C:30]2[N:31]3[C@H:34]([S:35][CH:36]=2)[C:33]([CH:14]([O:15][C:51](=[O:53])[CH3:52])[C:2]2[N:3]=[C:4]4[CH:13]=[N:12][C:11]5[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=5)[N:5]4[CH:1]=2)([Br:37])[C:32]3=[O:38])=[O:29])=[CH:24][CH:23]=1)([O-:21])=[O:20]

Participants

10

Reactant 6

HCID 311Citric AcidHCID 7918Acetic AnhydrideHCID 82241Magnesium BromideHCID 11280588(5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl esterHCID 13770471Imidazo[1,2-a]quinoxaline-2-carboxaldehydeHCID 865890494,4-Dimethylaminopyridine

Product 1

HCID 68707930(5R,6RS)-6-((RS)-Acetoxy imidazo[1,2-a]quinoxalin-2-ylmethyl)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid p-Nitrobenzyl Ester

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

A dry acetonitrile (33 mL) solution of imidazo[1,2-a]quinoxaline-2-carboxaldehyde (505 mg) was added to a dry acetonitrile (20 mL) solution of MgBr2 (1.1 g) under an nitrogen atmosphere at room temperature, and the mixture was stirred for 10 min. After addition of the dry THF (25 mL) solution of (5R,6S)-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester (931 mg), the mixture was cooled to −20° C. then triethylamine (0.8 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. The reaction mixture was stirred for 4 h at −20° C. and treated with 4,4-dimethylamino pyridine (58 mg) and acetic anhydride (0.44 mL) in one portion. The reaction mixture was warmed to 0° C. and stirred for 16 h at 0° C. 10% Citric acid aqueous solution (200 mL) was added to the reaction mixture and the aqueous layer was extracted with ethyl acetate (3×100 mL). The organic layer was washed with water, saturated sodium hydrogen carbonate and brine, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with CH2Cl2-acetone (50:1), and the title compound was obtained as a diastereomeric mixture (78:22, pale brown foamy amorphous, 1.0 g, 68.9%).

Workup

  1. stirringThe reaction mixture was stirred for 4 h at −20° C.
  2. temperatureThe reaction mixture was warmed to 0° C.
  3. stirringstirred for 16 h at 0° C
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
  5. washThe organic layer was washed with water, saturated sodium hydrogen carbonate and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography
  10. washeluted with CH2Cl2-acetone (50:1)

Sources & evidence

ORD record
ord-bf9608d2bac5441e89181dcc4ffec602
Source dataset
uspto-grants-2010_04
Patent number
US07691842B2

Reaction notes

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