3,4-dihydro-2H-pyran → (3r)-3-(Cyclopentylmethyl)-1-(tetrahydro-2h-pyran-2-yloxy)azetidin-2-one

HRID 1366375Notes

Reaction equation

HRID 1366375 reaction equation
[CH:1]1([CH2:6][C@@H:7]2[CH2:10][N:9]([O:11][CH2:12][C:13]3C=C[CH:16]=[CH:15][CH:14]=3)[C:8]2=[O:19])[CH2:5][CH2:4][CH2:3][CH2:2]1.[O:20]1C=CCCC1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C(O)C>[CH:1]1([CH2:6][C@@H:7]2[CH2:10][N:9]([O:11][CH:12]3[CH2:13][CH2:14][CH2:15][CH2:16][O:20]3)[C:8]2=[O:19])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 53718234(r)-1-(Benzyloxy)-3-(cyclopentylmethyl)azetidin-2-one

Product 1

HCID 66935931(3r)-3-(Cyclopentylmethyl)-1-(tetrahydro-2h-pyran-2-yloxy)azetidin-2-oneYield 100%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(3R)-3-(Cyclopentylmethyl)-1-[(phenylmethyl)oxy]-2-azetidinone (100 g, 386 mmol) was dissolved in ethanol (1.2 L), and the solution was degassed. Pd on C (10%, dry, 8 g) was added and the suspension was purged with hydrogen and stirred under a hydrogen atmosphere (balloon) until the reaction was complete by LC-MS (approximately 6 h). The suspension was then sparged with nitrogen, filtered through Celite, and evaporated to dryness. The resulting solid was redissolved in CH2Cl2 (1 L) and dihydropyran (70 mL, 767 mmol) was added, followed by pyridinium p-toluenesulfonate (PPTS, 5%, 4.85 g). The reaction mixture was stirred 3 days at room temperature, then concentrated and chromatographed on silica gel using 10-20% ethyl acetate in hexanes to provide (3R)-3-(cyclopentylmethyl)-1-(tetrahydro-2H-pyran-2-yloxy)-2-azetidinone as a colorless liquid (100%).

Workup

  1. customthe solution was degassed
  2. dry with materialPd on C (10%, dry, 8 g)
  3. additionwas added
  4. customthe suspension was purged with hydrogen
  5. customwas complete by LC-MS (approximately 6 h)
  6. customThe suspension was then sparged with nitrogen
  7. filtrationfiltered through Celite
  8. customevaporated to dryness
  9. dissolutionThe resulting solid was redissolved in CH2Cl2 (1 L)
  10. stirringThe reaction mixture was stirred 3 days at room temperature
  11. concentrationconcentrated
  12. customchromatographed on silica gel using 10-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-a06214db21494290b1a4fd1e6bb1f99c
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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