Phosphate → (6z)-6-(4,5,6,7-Tetrahydro-1,3a,3b,8-tetraaza-cyclopenta[a]indene-2-ylmethylene)-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid sodium salt

HRID 1744934Notes

Reaction equation

HRID 1744934 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[N:31]=[C:30]5[N:25]([CH2:26][CH2:27][CH2:28][CH2:29]5)[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[N:25]3[C:30]([CH2:29][CH2:28][CH2:27][CH2:26]3)=[N:31][C:23]=12

Participants

8

Reactant 4

HCID 1061PhosphateHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 68701663(5R, 6RS)-6-{(RS)-Acetoxy-[4,5,6,7-tetrahydro-1,3a,3b,8-tetraaza-cyclopenta[a]indene-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 68443685(6z)-6-(4,5,6,7-Tetrahydro-1,3a,3b,8-tetraaza-cyclopenta[a]indene-2-ylmethylene)-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid sodium saltYield 18%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

(5R, 6RS)-6-{(RS)-Acetoxy-[4,5,6,7-tetrahydro-1,3a,3b,8-tetraaza-cyclopenta[a]indene-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 (643.6 mg) was dissolved in THF (9 mL) and acetonitrile (4.2 mL). Freshly activated Zn dust (2.57 g) and 0.5 M phosphate buffer (pH 6.4, 13.2 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 3° C., and 1 N 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. The aqueous layer was concentrated to 20 mL under high vacuum at 35° C. The concentrate was applied to Diaion HP-21 (60 mL, Mitsubishi Kasei Co. Ltd.) resin column chromatography. After adsorbing, the column was eluted with water and then with 2.5–10% 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 (68 mg, 18%, pH 7.4). Mp 175° C. (dec); 1H-NMR (400 MHz, D2O) δ 1.85–2.03 (m, 4H), 2.85–2.99 (m, 2H), 4.07–4.14 (m, 2H), 6.34 (s, 1H), 6.74 (s, 1H), 6.76 (s, 1H), 7.28 (s, 1H).

Workup

  1. temperatureThe mixture was cooled to 3° C.
  2. filtrationfiltered through a pad of Celite
  3. washThe pad was washed with water
  4. concentrationThe aqueous layer was concentrated to 20 mL under high vacuum at 35° C
  5. washthe column was eluted with water
  6. concentrationThe combined fractions was concentrated under high vacuum at 35° C.

Sources & evidence

ORD record
ord-d38b2fd75f8b4e0097ac607d84a6eab2
Source dataset
uspto-grants-2006_03
Patent number
US07018997B2

Reaction notes

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