Acetic Anhydride → (5R,6RS)-6-[Acetoxy-(7-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,2-a]pyrazin-2-yl)-methyl]-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

HRID 1158867Notes

Reaction equation

HRID 1158867 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[CH2:6][N:5]2[CH:9]=[C:10]([CH:12]=[O:13])[N:11]=[C:4]2[CH2:3]1.[Mg+2].[Br-].[Br-].[N+:17]([C:20]1[CH:38]=[CH:37][C:23]([CH2:24][O:25][C:26]([C:28]2[N:29]3[C@H:32]([S:33][CH:34]=2)[C@@H:31]([Br:35])[C:30]3=[O:36])=[O:27])=[CH:22][CH:21]=1)([O-:19])=[O:18].[C:39](OC(=O)C)(=[O:41])[CH3:40]>CN(C)C1C=CN=CC=1.C(OCC)(=O)C.O.C(N(CC)CC)C.C1COCC1.C(#N)C>[N+:17]([C:20]1[CH:38]=[CH:37][C:23]([CH2:24][O:25][C:26]([C:28]2[N:29]3[C@H:32]([S:33][CH:34]=2)[C:31]([CH:12]([O:13][C:39](=[O:41])[CH3:40])[C:10]2[N:11]=[C:4]4[CH2:3][N:2]([CH3:1])[C:7](=[O:8])[CH2:6][N:5]4[CH:9]=2)([Br:35])[C:30]3=[O:36])=[O:27])=[CH:22][CH:21]=1)([O-:19])=[O:18]

Participants

11

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 219414037-Methyl-6-oxo-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde

Product 1

HCID 68688112(5R,6RS)-6-[Acetoxy-(7-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,2-a]pyrazin-2-yl)-methyl]-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

Reagents, catalysts & solvents 6

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

7-Methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,2-a]pyrazine-2-carbaldehyde (319 mg) was added to the dry acetonitrile (32 mL) solution of anhydrous MgBr2 (786 mg) under a nitrogen atmosphere at room temperature. The dry THF solution (32 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 (687 mg) was added to the mixture, cooled to −20° C., and triethylamine (0.60 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. The reaction mixture was stirred for 3 h at −20° C. and treated with 4-dimethylaminopyridine (44 mg) and acetic anhydride (0.35 mL) in one portion. The reaction mixture was warmed to 0° C. and stirred for 20 h at 0° C. The mixture was diluted with ethyl acetate and H2O. After separating organic layer, the aqueous layer was extracted with ethyl acetate. The organic layers were combined and washed with 5% citric acid aqueous solution 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 eluted with chloroform. The title compound was obtained as diastereo mixture (yellow amorphous solid; 410 mg, 38%).

Workup

  1. temperatureThe reaction mixture was warmed to 0° C.
  2. stirringstirred for 20 h at 0° C
  3. customAfter separating organic layer
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washwashed with 5% citric acid aqueous solution and brine
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. washeluted with chloroform

Sources & evidence

ORD record
ord-c17cd544fb634a66938326b593284d19
Source dataset
uspto-grants-2010_10
Patent number
US07812014B2

Reaction notes

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