Iodine → (R)-tert-Butyl 2-((R)-3-ethoxy-1-hydroxy-3-oxopropyl)pyrrolidine-1-carboxylate

HRID 53502

Reaction equation

HRID 53502 reaction equation
[C:1]([N:8]1[CH2:14][CH2:13][CH2:12][C@@H:9]1[CH:10]=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH2:15]([O:17][C:18](=[O:21])[CH2:19]Br)[CH3:16].II>[Zn].C1C=CC=CC=1>[C:4]([O:3][C:1]([N:8]1[CH2:14][CH2:13][CH2:12][CH:9]1[CH:10]([OH:11])[CH2:19][C:18]([O:17][CH2:15][CH3:16])=[O:21])=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 3

HCID 807IodineHCID 7748Ethyl bromoacetateHCID 7009153N-(tert-Butoxycarbonyl)-D-prolinal

Product 1

HCID 10379312(R)-tert-Butyl 2-((R)-3-ethoxy-1-hydroxy-3-oxopropyl)pyrrolidine-1-carboxylateYield 41%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 241BenzeneSolvent2×

Procedure

Freshly activated zinc powder (0.79 g, 12 mmol, Aldrich) and benzene (50 mL) were placed into a 250-mL two neck round bottom flask under N2. This flask was attached to a Dean-Stark apparatus and 25 mL of benzene was distilled into the trap. Under reflux, a solution of Boc- D-Prolinal (1.90 g, 9.5 mmol) and ethylbromoacetate (2.0 g, 12 mmol, Aldrich) was added dropwise. A crystal of iodine was added to initiate the reaction after half of the dropping solution was added. After complete addition, the mixture was refluxed for 3 hours, cooled, and carefully washed with 0.5 n HCl. The aqueous solution was extracted with ether (25 mL) and the combined organic solution was washed successively with water (30 mL) and saturated NaHCO3 (30 mL), then dried with anhydrous Na2SO4 and concentrated under vacuum. A yellow oil was chromatographed on silica (with hexane/ethyl acetate) to isolate a colourless oil (1.12 g, 41%).

Workup

  1. distillationwas distilled into the trap
  2. temperatureUnder reflux
  3. customthe reaction after half of the dropping solution
  4. additionwas added
  5. additionAfter complete addition
  6. temperaturethe mixture was refluxed for 3 hours
  7. temperaturecooled
  8. washcarefully washed with 0.5 n HCl
  9. extractionThe aqueous solution was extracted with ether (25 mL)
  10. washthe combined organic solution was washed successively with water (30 mL) and saturated NaHCO3 (30 mL)
  11. dry with materialdried with anhydrous Na2SO4
  12. concentrationconcentrated under vacuum
  13. customA yellow oil was chromatographed on silica (with hexane/ethyl acetate)

Sources & evidence

ORD record
ord-9ecbb96f21e2420894d8a85170a8845d
Source dataset
uspto-grants-1997_04
Patent number
US05620959

Linked notes

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