(R)-tert-butyl 2-(2-oxoethyl)pyrrolidine-1-carboxylate → (2R)-tert-butyl 2-(2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl)pyrrolidine-1-carboxylate

HRID 2279588Notes

Reaction equation

HRID 2279588 reaction equation
[O:1]=[CH:2][CH2:3][C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].[Cl:16][C:17]1[CH:18]=[C:19]([Mg]Br)[CH:20]=[CH:21][C:22]=1[F:23]>C1COCC1>[Cl:16][C:17]1[CH:18]=[C:19]([CH:2]([OH:1])[CH2:3][C@H:4]2[CH2:8][CH2:7][CH2:6][N:5]2[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH:20]=[CH:21][C:22]=1[F:23]

Participants

4

Reactant 2

HCID 86328555(R)-tert-butyl 2-(2-oxoethyl)pyrrolidine-1-carboxylateHCID 178505834HCID 178505834, compound

Product 1

HCID 86705571(2R)-tert-butyl 2-(2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl)pyrrolidine-1-carboxylateYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-tert-butyl 2-(2-oxoethyl)pyrrolidine-1-carboxylate (A. Furstner and J. W. L. Kennedy, Chem.—Eur. J. 2006 12(28):7398-7410) in THF cooled to −78° C. was added (3-chloro-4-fluorophenyl)magnesium bromide (0.720 mL, 0.360 mmol) and the reaction was warmed to RT for 1 h. The reaction was quenched with water and extracted with EtOAc. The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated to afford an oil which was purified by SiO2 chromatography to afford 0.0745 g (72%) of (2R)-tert-butyl 2-(2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl)pyrrolidine-1-carboxylate (301) as a clear oil.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford an oil which
  8. customwas purified by SiO2 chromatography

Sources & evidence

ORD record
ord-d5bc32f843414947bf10a59ec9b99c67
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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