Phosphate → (6z)-6-(5h-Imidazo[2,1-a]isoindol-2-ylmethylene)-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid sodium salt

HRID 638866Notes

Reaction equation

HRID 638866 reaction equation
[N+](C1C=CC(C[O:9][C:10]([C:12]2[N:13]3[C@H:16]([S:17][CH:18]=2)[C:15]([CH:20](OC(=O)C)[C:21]2[N:22]=[C:23]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[CH2:25][N:24]4[CH:32]=2)(Br)[C:14]3=[O:37])=[O:11])=CC=1)([O-])=O.P([O-])([O-])([O-])=O.[OH-].[Na+:46].C(OCC)(=O)C>C1COCC1.C(#N)C.[Zn]>[Na+:46].[N:22]1[C:21](/[CH:20]=[C:15]2\[CH:16]3[N:13]([C:14]\2=[O:37])[C:12]([C:10]([O-:11])=[O:9])=[CH:18][S:17]3)=[CH:32][N:24]2[CH2:25][C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:23]=12

Participants

8

Reactant 4

HCID 1061PhosphateHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 68443556(5R,6RS)-6-[(RS)-Acetoxy-(5H-imidazo[2,1-a]isoindol-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

Product 1

HCID 68444698(6z)-6-(5h-Imidazo[2,1-a]isoindol-2-ylmethylene)-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid sodium saltYield 58%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

(5R,6RS)-6-[(RS)-Acetoxy-(5H-imidazo[2,1-a]isoindol-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 (1.5 g) was dissolved in THF (21 mL) and acetonitrile (9.8 mL). Freshly activated Zn dust (6 g) and 0.5 M phosphate buffer (pH 6.4, 30.8 mL) were added to the reaction mixture. The reaction vessel was covered with foil to exclude light. The mixture was vigorously stirred for 2 h at room temperature. The mixture was cooled to 9° C., and 1 M NaOH aqueous solution was added to adjust pH to 7.5. The reaction solution was mixed with ethyl acetate and filtered through a pad of Celite. The pad was washed with water and the aqueous layer was separated. The aqueous layer was concentrated to 25 mL under high vacuum at 35° C. The concentrate was applied to Diaion HP-21 (100 mL, Mitsubishi Kasei Co. Ltd.) resin column chromatography. After adsorbing, the column was eluted with water and then with 5-15% acetonitrile-water. The combined fractions was concentrated under high vacuum at 35° C. and lyophilized to give the title compound as a yellow amorphous solid (527 mg, 58%). Mp 170° C. (dec); 1H NMR (400 MHz, D2O) δ 4.62 (s, 2H), 6.27 (s, 1H), 6.56 (s, 1H), 6.78 (s, 1H), 7.22-7.31 (m, 4H), 7.52 (d, 1H, J=6.7 Hz).

Workup

  1. temperatureThe mixture was cooled to 9° C.
  2. filtrationfiltered through a pad of Celite
  3. washThe pad was washed with water
  4. customthe aqueous layer was separated
  5. concentrationThe aqueous layer was concentrated to 25 mL under high vacuum at 35° C
  6. washthe column was eluted with water
  7. concentrationThe combined fractions was concentrated under high vacuum at 35° C.

Sources & evidence

ORD record
ord-ae27a61ae3f240848fd8e3e8f29e5e2a
Source dataset
uspto-grants-2010_04
Patent number
US07691842B2

Reaction notes

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