Hydrochloric Acid → HCID 58781982, compound

HRID 1374397Notes

Reaction equation

HRID 1374397 reaction equation
C(OC([N:7]1[CH2:12][CH:11]=[C:10]([C:13]2[N:14]=[C:15]([S:18][C:19]3[C@H:25]([CH3:26])[C@H:24]4[N:21]([C:22](=[O:34])[C@@H:23]4[C@H:27]([O:29][Si](C)(C)C)[CH3:28])[C:20]=3[C:35]([O:37]CC=C)=[O:36])[S:16][CH:17]=2)[CH2:9][C@H:8]1[CH2:41][Cl:42])=O)C=C.Cl.C(=O)([O-])O.[Na+].C([SnH](CCCC)CCCC)CCC.P([O-])([O-])([O-])=O>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.ClCCl.C(O)(=O)C.O>[OH:29][C@@H:27]([C@H:23]1[C:22](=[O:34])[N:21]2[C@@H:24]1[C@@H:25]([CH3:26])[C:19]([S:18][C:15]1[S:16][CH:17]=[C:13]([C:10]3[CH2:9][C@@H:8]([CH2:41][Cl:42])[NH:7][CH2:12][CH:11]=3)[N:14]=1)=[C:20]2[C:35]([OH:37])=[O:36])[CH3:28]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 1061PhosphateHCID 5948TributylstannaneHCID 516892Sodium BicarbonateHCID 86592511HCID 86592511, compound

Product 1

HCID 58781982HCID 58781982, compoundYield 59.5%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of allyl (4R,5S,6S)-3-({4-[(2S)-1-[(allyloxy)carbonyl]-2-(chloromethyl)-1,2,3,6-tetrahydro-4-pyridinyl]-1,3-thiazol-2-yl}sulfanyl)-4-methyl-7-oxo-6-{(1R)-1-[(trimethylsilyl)oxy]ethyl}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (54 mg, 0.083 mmol) in THF (4 ml) was added at 0° C. water (7 ml) and then the solution was adjusted to pH about 2 with 1N hydrochloric acid and stirred for 15 minutes. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution. The solution was adjusted to pH 7.5 and extracted twice with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After removal of the solvent in vacuo, the residue was dissolved in dichloromethane (2 ml). To the solution were added at 0° C. acetic acid (12 μl), tributyltin hydride (0.23 ml) and bis(triphenylphosphine)palladium chloride (5.8 mg, 0.014 mmol) and the mixture was stirred at the same temperature for 10 minutes. To the reaction mixture were added phosphate buffer (50 mM, pH7, 25 ml) and dichloromethane (20 ml). After separation of the aqueous layer, the dichloromethane layer was extracted with water and the aqueous layer was washed twice with dichloromethane (3 ml). The organic solvent in the aqueous layer was evaporated under reduced pressure, and the residue was purified by polymer chromatography (CHP-20P). The fractions eluted with an 1–3% aqueous THF solution were combined and lyophilized to give (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-({4-[(2S)-2-(chloromethyl)-1,2,3,6-tetrahydro-4-pyridinyl]-1,3-thiazol-2-yl}sulfanyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (22.5 mg, 46%) as a white amorphous.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. customAfter removal of the solvent in vacuo
  5. dissolutionthe residue was dissolved in dichloromethane (2 ml)
  6. stirringthe mixture was stirred at the same temperature for 10 minutes
  7. customAfter separation of the aqueous layer
  8. extractionthe dichloromethane layer was extracted with water
  9. washthe aqueous layer was washed twice with dichloromethane (3 ml)
  10. customThe organic solvent in the aqueous layer was evaporated under reduced pressure
  11. customthe residue was purified by polymer chromatography (CHP-20P)
  12. washThe fractions eluted with an 1–3% aqueous THF solution

Sources & evidence

ORD record
ord-670761e3d2f84522842d54182070d10d
Source dataset
uspto-grants-2007_01
Patent number
US07163936B2

Reaction notes

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