1-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl ester → Tert-butyl 2-(2,5-difluorophenyl)-2-hydroxypyrrolidine-1-carboxylate

HRID 1890680Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[Mg]Cl.[O:11]=[C:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].[Cl-].[Mg+2].[Cl-]>C1COCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:12]1([OH:11])[CH2:16][CH2:15][CH2:14][N:13]1[C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18]

Participants

Conditions

Temperature: -78 °C

Procedure

In step 6A-1, (2,5-difluorophenyl)magnesium chloride (6-1) was added drop-wise to a solution of tert-butyl 2-oxopyrrolidine-1-carboxylate (6-2) (9.6 g, 52 mmol) in THF under argon at −78° C. A maximum of 5 mL aliquots was used to minimize the temperature increase of the magnesium chloride reagent. The resulting solution was then stirred at −78° C. for one hour. The solution was then warmed to room temperature and quenched with concentrated HCl (4 mL). The solvent was then removed using a rotary evaporator resulting in a light yellow residue. The residue was then reconstituted in ethyl acetate and extracted with brine (3×150 mL). The organic layer was then dried using sodium sulfate. The ethyl acetate was removed yielding tert-butyl 2-(2,5-difluorophenyl)-2-hydroxypyrrolidine-1-carboxylate (6-3) as a light yellow oil. m/z=300 [M+1] The product was used without further purification.

Workup

temperatureThe solution was then warmed to room temperature
customquenched with concentrated HCl (4 mL)
customThe solvent was then removed
customa rotary evaporator
customresulting in a light yellow residue
extractionextracted with brine (3×150 mL)
customThe organic layer was then dried
customThe ethyl acetate was removed

Sources & evidence

ORD record: ord-50b8c94e77eb4447b9903fbed18ed613
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507488B2

Reaction notes

Loading…