Citric Acid → HCID 87456424, compound

HRID 2216557Notes

Reaction equation

HRID 2216557 reaction equation
[N+:1]([C:4]1[CH:24]=[CH:23][C:7]([CH2:8][O:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]3[CH:18]=[C:19]([CH:21]=[O:22])[N:20]=[C:14]3[CH2:13]2)=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[Mg+2].[Br-].[Br-].[N+:28]([C:31]1[CH:49]=[CH:48][C:34]([CH2:35][O:36][C:37]([C:39]2[N:40]3[C@H:43]([S:44][CH:45]=2)[C@@H:42]([Br:46])[C:41]3=[O:47])=[O:38])=[CH:33][CH:32]=1)([O-:30])=[O:29].CNC1(NC)C=CN=CC1.[C:60](OC(=O)C)(=[O:62])[CH3:61].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(N(CC)CC)C.C1COCC1.C(#N)C>[N+:28]([C:31]1[CH:49]=[CH:48][C:34]([CH2:35][O:36][C:37]([C:39]2[N:40]3[C@H:43]([S:44][CH:45]=2)[C:42]([CH:21]([O:22][C:60](=[O:62])[CH3:61])[C:19]2[N:20]=[C:14]4[CH2:13][N:12]([C:10]([O:9][CH2:8][C:7]5[CH:23]=[CH:24][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=5)=[O:11])[CH2:17][CH2:16][N:15]4[CH:18]=2)([Br:46])[C:41]3=[O:47])=[O:38])=[CH:33][CH:32]=1)([O-:30])=[O:29]

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 21941360HCID 21941360, compoundHCID 865890494,4-Dimethylaminopyridine

Product 1

HCID 87456424HCID 87456424, compound

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

The dry acetonitrile (25 mL) solution of 7-p-nitrobenzyloxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde (1.6 g) was added to the dry acetonitrile (55 mL) solution of MgBr2 (2.2 g) under an nitrogen atmosphere at room temperature then the mixture was stirred for 10 min. The dry THF (80 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 (1.8 g) was added, the mixture was cooled to −20° C. then triethylamine (1.6 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 4,4-dimethylamino pyridine (58.3 mg) and acetic anhydride (0.89 mL) in one portion. The reaction mixture was warmed to 0° C. and stirred for 15 h at 0° C. 10% Citric acid aqueous solution (320 mL) was added to the reaction mixture and the aqueous layer was extracted with ethyl acetate (3×160 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 applied to silica gel column chromatography, eluted with CH2Cl2-acetone (20:1), and the title compound was obtained as two diastereo mixture (81:19, brown foamy amorphous solid. Yield: 2.1 g, 59.9%.

Workup

  1. stirringThe reaction mixture was stirred for 3 h at −20° C.
  2. temperatureThe reaction mixture was warmed to 0° C.
  3. stirringstirred for 15 h at 0° C
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×160 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. washeluted with CH2Cl2-acetone (20:1)

Sources & evidence

ORD record
ord-c1390173f09e4f6386cc4c922ab72fb2
Source dataset
uspto-grants-2006_09
Patent number
US07112582B2

Reaction notes

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