Phosphate → HCID 21057710, compound

HRID 2216616Notes

Reaction equation

HRID 2216616 reaction equation
P([O-])([O-])([O-])=[O:2].[O:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.C(#N)C.[N+](C1C=CC(COC(C2N3[C@H](SC=2)C(C(OC(=O)C)[C:34]2C=[C:37]4[S:38][CH2:39][CH2:40][N:36]4[N:35]=2)(Br)C3=O)=O)=CC=1)([O-])=O>[Zn].C(OCC)(=O)C>[CH2:10]([O:6][C:7]([C:8]1[CH:34]=[N:35][N:36]2[CH2:40][CH2:39][S:38][C:37]=12)=[O:2])[CH3:9]

Participants

7

Reactant 4

HCID 1061PhosphateHCID 6342AcetonitrileHCID 8028TetrahydrofuranHCID 68688939HCID 68688939, compound

Product 1

HCID 21057710HCID 21057710, compoundYield 39.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Freshly activated Zn dust (37.4 g) was added rapidly with 0.5 mol/l phosphate buffer (pH 6.5, 196 ml) to tetrahydrofuran (134 ml) and acetonitrile (62 ml) solution of (5R)-6-[acetoxy-(2,3-dihydropyrazolo[5,1-b]thiazol-6-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester. The reaction vessel was covered with foil to exclude light. The reaction mixture was vigorously stirred for 1.5 hours at room temperature. The reaction mixture was cooled at 0° C., and then the pH was adjusted to 8.0. ethyl acetate (100 ml) was added to the reaction mixture. The mixture was filtered through a pad of Celite and the pad was washed with water (300 ml). The aqueous layer was separated and then the organic layer was extracted with 0.5 mol/l phosphate buffer (pH 6.5, 2×50 ml). The pH of the combined aqueous layer was adjusted to 8.0 and the mixture was concentrated to 426 g. The concentrate was adjust pH to 8.0 and applied to Diaion HP-21 resin (540 ml, Mitsubishi Kasei Co. Ltd.) column chromatography. After adsorbing, the column was eluted with water (1 bed volume) and then 5% (2 bed volume), 10% (2 bed volume) and 20% acetonitrile aqueous solution. The combined active fractions were concentrated under high vacuum at 35° C. and lyophilized to give the title compound as a orange amorphous solid (2.09 g, 39.2%, pH 7.10).

Workup

  1. temperatureThe reaction mixture was cooled at 0° C.
  2. filtrationThe mixture was filtered through a pad of Celite
  3. washthe pad was washed with water (300 ml)
  4. customThe aqueous layer was separated
  5. extractionthe organic layer was extracted with 0.5 mol/l phosphate buffer (pH 6.5, 2×50 ml)
  6. concentrationthe mixture was concentrated to 426 g
  7. washthe column was eluted with water (1 bed volume)
  8. concentrationThe combined active fractions were concentrated under high vacuum at 35° C.

Sources & evidence

ORD record
ord-e0991b6294af4f3eb6a1294935e7e532
Source dataset
uspto-grants-2006_09
Patent number
US07112582B2

Reaction notes

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