3,4-dihydro-2H-pyran → HCID 57815104, compound

HRID 1160460Notes

Reaction equation

HRID 1160460 reaction equation
[CH3:1][O:2][C:3](=[O:40])[C@H:4]([OH:39])[C@@H:5]([NH:13][C:14](=[O:38])[C:15]1[CH:20]=[C:19]([C:21]([NH:23][C@@H:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH3:25])=[O:22])[CH:18]=[C:17]([N:32]([CH3:37])[S:33]([CH3:36])(=[O:35])=[O:34])[CH:16]=1)[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[O:41]1[CH:46]=[CH:45][CH2:44][CH2:43][CH2:42]1.[NH+]1C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[CH3:1][O:2][C:3](=[O:40])[C@H:4]([O:39][CH:42]1[CH2:43][CH2:44][CH2:45][CH2:46][O:41]1)[C@@H:5]([NH:13][C:14](=[O:38])[C:15]1[CH:20]=[C:19]([C:21]([NH:23][C@@H:24]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH3:25])=[O:22])[CH:18]=[C:17]([N:32]([CH3:37])[S:33]([CH3:36])(=[O:35])=[O:34])[CH:16]=1)[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 22033616Pyridinium.p-toluenesulfonateHCID 57815131HCID 57815131, compound

Product 1

HCID 57815104HCID 57815104, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The (2R,3S)-2-hydroxy-3-{[3-[methyl(methylsulfonyl)amino]-5-({[(1R)-1-phenylethyl]amino}carbonyl)benzoyl]amino}-4-phenylbutanoic acid methylester obtained in Reference Example 25 2.30 g (4.06 mmol) was dissolved in tetrahydrofuran 8 mL and thereto were added 3,4-dihydro-2H-pyrane 4.80 mL and p-toluenesulfonic acid pyridinium 204 mg (0.81 mmol) and the mixture was stirred under reflux for 8 hours. After distillating tetrahydrofuran off, the residue was extracted by adding ethyl acetate and 5% aqueous sodium carbonate solution. The organic layer was washed with an aqueous saturated sodium chloride solution and dried on magnesium sulfate, filtered and concentrated. The concentrated residue was purified by a column chromatography on silica gel (eluted with chloroform-methanol system) and recrystallized from a mixed solvent of ethyl acetate and hexane. A precipitated material was collected by filtering and dried to give 1.81 g (2.78 mmol) of the title compound (yield: 69%).

Workup

  1. temperatureunder reflux for 8 hours
  2. extractionwas extracted
  3. additionby adding ethyl acetate and 5% aqueous sodium carbonate solution
  4. washThe organic layer was washed with an aqueous saturated sodium chloride solution
  5. customdried on magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe concentrated residue was purified by a column chromatography on silica gel (eluted with chloroform-methanol system)
  9. customrecrystallized from a mixed solvent of ethyl acetate and hexane
  10. customA precipitated material was collected
  11. filtrationby filtering
  12. customdried

Sources & evidence

ORD record
ord-54dfb36c9f68480480a1beb24298945d
Source dataset
uspto-grants-2010_10
Patent number
US07816387B2

Reaction notes

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