HCID 21941358, compound → HCID 21941469, compound

HRID 1158929Notes

Reaction equation

HRID 1158929 reaction equation
[S:1]1[CH2:5][CH2:4][N:3]=[C:2]1[N:6]1[CH2:11][CH2:10][N:9]2[N:12]=[C:13]([CH2:15][OH:16])[CH:14]=[C:8]2[CH2:7]1>[O-2].[Mn+4].[O-2].C(Cl)(Cl)Cl>[S:1]1[CH2:5][CH2:4][N:3]=[C:2]1[N:6]1[CH2:11][CH2:10][N:9]2[N:12]=[C:13]([CH:15]=[O:16])[CH:14]=[C:8]2[CH2:7]1

Participants

4

Reactant 1

HCID 21941358HCID 21941358, compound

Product 1

HCID 21941469HCID 21941469, compound

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 6212ChloroformSolvent

Procedure

The activated manganese (IV) oxide (16.75 g) was added to the mixture of chloroform (180 ml) solution of [5-(4,5-dihydrothiazol-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl]-methanol (3.35 g) at room temperature. The reaction mixture was refluxed for 1 hour. After refluxing, the mixture was filtered through a pad of Celite and the filtrate was concentrated under reduced pressure. The residue was dried in vacuo and the crude 5-(4,5-dihydrothiazol-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carbaldehyde was obtained as a colorless solid. The crude aldehyde thus obtained (2.56 g) was added to a dry acetonitrile (200 ml) solution of MgBr2 (7.36 g) under a nitrogen atmosphere at room temperature then the mixture was stirred for 10 minutes. A dry THF (200 ml) solution of WLJ 20,014 (4.16 g) was added and the mixture was cooled to −20° C. Then triethylamine (11.3 ml) was added in one portion. The reaction vessel was covered with foil to exclude light. The reaction mixture was stirred for 1.5 hours at −20° C. and treated with 4-dimethylaminopyridine (132 mg) and acetic anhydride (4.2 ml) in one portion. The reaction mixture was warmed to 0° C. and stirred for 20 hours 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 eluted with n-hexane-AcOEt (1:2) and chloroform-methanol (9:1). The (5R,6RS)-6-{(RS)-acetoxy-[5-(4,5-dihydrothiazol-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-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 was obtained (5.41 g, 75.4%).

Workup

  1. temperatureThe reaction mixture was refluxed for 1 hour
  2. temperatureAfter refluxing
  3. filtrationthe mixture was filtered through a pad of Celite
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was dried in vacuo

Sources & evidence

ORD record
ord-893c0a6c418440808bf21c7bd4312bbd
Source dataset
uspto-grants-2010_10
Patent number
US07812014B2

Reaction notes

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