Tetrahydrofuran → HCID 58507546, compound

HRID 1427730Notes

Reaction equation

HRID 1427730 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C:13](=[O:18])NCOC)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[C:24]1([Mg]Br)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C:13](=[O:18])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 66924544HCID 66924544, compoundHCID 178418255HCID 178418255, compound

Product 1

HCID 58507546HCID 58507546, compound

Conditions

Temperature
0 °C

Procedure

(S)-3-(Methoxymethylcarbamoyl)pyrrolidine-1-carboxylic acid t-butyl ester (400 mg, 1.6 mmol) and THF (10 mL, 0.1 mol) were combined under nitrogen. The solution was cooled at 0° C. using an ice bath. 1.0 M of Phenylmagnesium bromide in THF (7.0 mL, 7.0 mmol) was added dropwise over 5 minutes. The mixture was slowly warmed to room temperature and stirred for 30 minutes. The mixture was cooled in an ice bath and the reaction was quenched by the slow addition of water (15 mL). The mixture was extracted with EtOAc (1×100 mL), and the organic layer was washed with sat. NaCl (50 mL), dried over Na2SO4, filtered, and concentrated to yield 849 mg of crude product, which was purified by flash chromatography (12 g column, 20-100% EtOAc in hexanes over 17 minutes), and placed under high vacuum for 15 minutes to yield 372 mg of the title compound as a clear oil.

Workup

  1. temperatureThe mixture was slowly warmed to room temperature
  2. temperatureThe mixture was cooled in an ice bath
  3. customthe reaction was quenched by the slow addition of water (15 mL)
  4. extractionThe mixture was extracted with EtOAc (1×100 mL)
  5. washthe organic layer was washed with sat. NaCl (50 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield 849 mg of crude product, which
  10. customwas purified by flash chromatography (12 g column, 20-100% EtOAc in hexanes over 17 minutes)
  11. waitplaced under high vacuum for 15 minutes

Sources & evidence

ORD record
ord-d977f6eecfc547679d1b0fe393346ac4
Source dataset
uspto-grants-2015_01
Patent number
US08933249B2

Reaction notes

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