Acetic Anhydride → (5R,6RS)-6-[(RS)-Acetoxy(7-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid 4-nitrobenzyl Ester

HRID 1158849Notes

Reaction equation

HRID 1158849 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]2[CH:8]=[C:9]([CH:11]=[O:12])[N:10]=[C:4]2[CH2:3]1.[Mg+2].[Br-].[Br-].[N+:16]([C:19]1[CH:37]=[CH:36][C:22]([CH2:23][O:24][C:25]([C:27]2[N:28]3[C@H:31]([S:32][CH:33]=2)[C@@H:30]([Br:34])[C:29]3=[O:35])=[O:26])=[CH:21][CH:20]=1)([O-:18])=[O:17].[C:38](OC(=O)C)(=[O:40])[CH3:39]>C(OCC)(=O)C.CCN(CC)CC.C1COCC1.C(#N)C>[N+:16]([C:19]1[CH:37]=[CH:36][C:22]([CH2:23][O:24][C:25]([C:27]2[N:28]3[C@H:31]([S:32][CH:33]=2)[C:30]([CH:11]([O:12][C:38](=[O:40])[CH3:39])[C:9]2[N:10]=[C:4]4[CH2:3][N:2]([CH3:1])[CH2:7][CH2:6][N:5]4[CH:8]=2)([Br:34])[C:29]3=[O:35])=[O:26])=[CH:21][CH:20]=1)([O-:18])=[O:17]

Participants

9

Reactant 4

HCID 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 118471317-Methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde

Product 1

HCID 11847281(5R,6RS)-6-[(RS)-Acetoxy(7-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid 4-nitrobenzyl Ester

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

7-Methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde (1.19 g) was added to the dry acetonitrile (97 mL) solution of anhydrous MgBr2 (4.05 g) under a nitrogen atmosphere at room temperature. The dry THF solution (97 mL) 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 (3.32 g) was added to the mixture, cooled to −20° C., and Et3N (3.0 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. The reaction mixture was stirred for 4.5 h at −20° C. and treated with acetic anhydride (1.36 mL) in one portion. The reaction mixture was warmed to 0° C. and stirred for 17 h at 0° C. The mixture was diluted with ethyl acetate and washed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate, and brine. The organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, then the column was eluted with CHCl3-acetone (9/1˜2/1). The titled compound was obtained as two diastereo mixture. Red oil, Yield: 1.13 g.

Workup

  1. temperatureThe reaction mixture was warmed to 0° C.
  2. stirringstirred for 17 h at 0° C
  3. washwashed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate, and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. washthe column was eluted with CHCl3-acetone (9/1˜2/1)

Sources & evidence

ORD record
ord-62e875f9a9204c41b23e07a1d3ed761c
Source dataset
uspto-grants-2010_10
Patent number
US07812014B2

Reaction notes

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