Phosphate → (5R,6Z)-6-[(5-methyl-7,8-dihydro-6H-cyclopenta[e][1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methylene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

HRID 638880Notes

Reaction equation

HRID 638880 reaction equation
C(O[CH:5]([C:28]1[N:40]=[C:31]2[N:32]=[C:33]([CH3:39])[C:34]3[CH2:38][CH2:37][CH2:36][C:35]=3[N:30]2[N:29]=1)[C:6]1(Br)[C:12](=[O:13])[N:11]2[C@@H:7]1[S:8][CH:9]=[C:10]2[C:14]([O:16]CC1C=CC([N+]([O-])=O)=CC=1)=[O:15])(=O)C.C(#N)C.P([O-])([O-])([O-])=O>C1COCC1.[Pd]>[CH3:39][C:33]1[C:34]2[CH2:38][CH2:37][CH2:36][C:35]=2[N:30]2[N:29]=[C:28](/[CH:5]=[C:6]3\[C@@H:7]4[N:11]([C:12]\3=[O:13])[C:10]([C:14]([OH:16])=[O:15])=[CH:9][S:8]4)[N:40]=[C:31]2[N:32]=1

Participants

6

Reactant 3

HCID 1061PhosphateHCID 6342AcetonitrileHCID 696084294-Nitrobenzyl (5r)-6-[(acetyloxy)(5-methyl-7,8-dihydro-6h-cyclopenta[e] [1,2,4]triazolo [1,5-a]pyrimidin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

Product 1

HCID 10452183(5R,6Z)-6-[(5-methyl-7,8-dihydro-6H-cyclopenta[e][1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methylene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
3 °C

Procedure

4-nitrobenzyl (5R)-6-[(acetyloxy)(5-methyl-7,8-dihydro-6H-cyclopenta[e][1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (200 mg, 0.31 mmol) was dissolved in THF (20 mL) and acetonitrile (20 mL) and phosphate buffer (6.5 pH) (20 ml) and hydrogenated over Pd/C (10%) (200 mg) under 40 psi pressure. At the end, reaction mixture was filtered, cooled to 3° C., and 0.1 N NaOH was added to adjust the pH to 8.5. The filtrate was washed with ethyl acetate and the aqueous layer was separated. The aqueous layer was concentrated under high vacuum at 35° C. to give a yellow precipitate. The product was purified by HP21 resin reverse phase column chromatography. Initially the column was eluted with deionized water (2 L) and latter with 10% acetonitrile:water. The fractions containing the product were collected and concentrated under reduced pressure at room temperature. The yellow solid was washed with acetone, filtered and dried. Yield: 15 mg, 13%; as yellow crystals; mp 250° C. (Dec); (M+H+Na) 378. 1H NMR (DMSO-d6) δ 6.80 (s, 1H), 6.76 (s, 1H), 6.25 (s, 1H), 3.24 (m, 2H), 2.96 (m, 2H), 2.49 (s, 3H), 2.25 (m, 2H).

Workup

  1. customAt the end, reaction mixture
  2. filtrationwas filtered
  3. addition0.1 N NaOH was added
  4. washThe filtrate was washed with ethyl acetate
  5. customthe aqueous layer was separated
  6. concentrationThe aqueous layer was concentrated under high vacuum at 35° C.
  7. customto give a yellow precipitate
  8. customThe product was purified by HP21 resin reverse phase column chromatography
  9. washInitially the column was eluted with deionized water (2 L) and latter with 10% acetonitrile
  10. additionThe fractions containing the product
  11. customwere collected
  12. concentrationconcentrated under reduced pressure at room temperature
  13. washThe yellow solid was washed with acetone
  14. filtrationfiltered
  15. customdried

Sources & evidence

ORD record
ord-dc618120724646d1b92ead9f11b93bd9
Source dataset
uspto-grants-2010_04
Patent number
US07691842B2

Reaction notes

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