Acetic Acid → HCID 131718796, compound

HRID 1492325Notes

Reaction equation

HRID 1492325 reaction equation
[O:1]=[C:2]1[N:9]2[C@H:5]([CH2:6][O:7][C@@H:8]2[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:4][CH2:3]1.C([N-]C(C)C)(C)C.[Li+].[C:24]([O:28][C:29]([N:31]1[CH2:37][C@H:36]([O:38][Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])[CH2:35][C@H:32]1[CH:33]=[O:34])=[O:30])([CH3:27])([CH3:26])[CH3:25].C(O)(=O)C>O1CCCC1>[C:24]([O:28][C:29]([N:31]1[CH2:37][C@H:36]([O:38][Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])[CH2:35][C@H:32]1[CH:33]([OH:34])[CH:3]1[C:2](=[O:1])[N:9]2[C@H:5]([CH2:6][O:7][C@@H:8]2[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:4]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 395160(3R,7aS)-3-Phenyltetrahydro-3H,5H-pyrrolo[1,2-c][1,3]oxazol-5-oneHCID 2724682Lithium diisopropylamideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylate

Product 1

HCID 131718796HCID 131718796, compoundYield 11.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (2R, 5S)-8-oxo-2-phenyl-3-oxa-1-azabicyclo[3.3.0]octane (50 g, 246 mmol, J. Org. Chem., 51, 3140 (1986)) in tetrahydrofuran (1500 ml), lithium diisopropylamide (2M tetrahydrofuran-heptane solution, 147.6 ml, 295.2 mmol) was dropwise added at -78° C., and the reaction solution was stirred at the same temperature for 30 minutes. A solution of (2S, 4R)-N-tert-butoxycarbonyl-4-tert-butyldimethylsiloxyprolinal (61.0 g, 245.9 mmol) in tetrahydrofuran (400 ml) was dropwise added thereto, and the reaction solution was stirred at the same temperature for 30 minutes. Acetic acid (17.6 ml, 307.5 mmol) was dropwise added to the reaction solution. Then, the dry ice bath was removed and the reaction mixture solution was stirred for 30 minutes. To the reaction solution, ethyl acetate and 5% sodium hydrogen carbonate aqueous solution were added and the solution mixture was subjected to liquid separation and the aqueous layer was extracted with ethyl acetate. The organic layers were put together and washed with a saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. Ethyl acetate and n-hexane were added to the residue and the precipitated crystal was collected by filtration to obtain (2R, 5S)-7-[[(2S, 4R)-N-tert-butoxycarbonyl-4-(tert-butyldimethylsiloxy)pyrrolidin-2-yl](hydroxy)methyl]-8-oxo-2-phenyl-3-oxa-1azabicyclo[3.3.01octane diastereomer A (14.0 g, yield: 11.3%). The filtrate was concentrated to obtain an oily diastereomer mixture (114.7 g, yield: 87.5%).

Workup

  1. stirringthe reaction solution was stirred at the same temperature for 30 minutes
  2. customThen, the dry ice bath was removed
  3. stirringthe reaction mixture solution was stirred for 30 minutes
  4. additionTo the reaction solution, ethyl acetate and 5% sodium hydrogen carbonate aqueous solution were added
  5. customthe solution mixture was subjected to liquid separation
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washwashed with a saturated sodium chloride aqueous solution
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. additionEthyl acetate and n-hexane were added to the residue
  11. filtrationthe precipitated crystal was collected by filtration

Sources & evidence

ORD record
ord-ee37a0d307c747e5814217a06496d078
Source dataset
uspto-grants-1994_12
Patent number
US05373002

Reaction notes

Loading…