Reaction #1563950

Reaction equation

tert-butyl 2-oxopyrrolidine-1-carboxylate

isopropyl magnesium chloride

5-bromo-7-fluoro-2,3-dihydrobenzo[b][1,4]dioxine

→

tert-butyl 5-(7-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-2,3-dihydro-1H-pyrrole-1-carboxylate

Solvents

THF

THF

THF

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was cooled again to −45° C.
2. 2
   Temperaturemaintaining the temperature at −45° C
3. 3
   TemperatureThe reaction mixture was warmed to 25° C.
4. 4
   Otherquenched with saturated NH4Cl solution (100 mL)
5. 5
   ExtractionThe reaction mixture was extracted with ethyl acetate (3×30 mL)
6. 6
   Dryingthe organic layer was dried over anhydrous sodium sulphate
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   Otherpurified by column chromatography (using silica gel and 20% ethyl acetate Hexane as eluent)

Procedure

A solution of isopropyl magnesium chloride in THF (2M, 5.39 mL, 10.78 mmol) was added to a solution of 5-bromo-7-fluoro-2,3-dihydrobenzo[b][1,4]dioxine (Int-53) (1 g, 4.31 mmol) in THF (10 mL) at −45° C. drop-wise and then allowed it to warm up to 5° C. over a period of 1 h. The reaction mixture was cooled again to −45° C. and a solution of tert-butyl 2-oxopyrrolidine-1-carboxylate (1.6 g, 8.62 mmol) in THF (10 mL) was added drop-wise maintaining the temperature at −45° C. The reaction mixture was warmed to 25° C. and stirred for 1 h and then quenched with saturated NH4Cl solution (100 mL). The reaction mixture was extracted with ethyl acetate (3×30 mL) and the organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure and purified by column chromatography (using silica gel and 20% ethyl acetate Hexane as eluent) to afford tert-butyl 5-(7-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-2,3-dihydro-1H-pyrrole-1-carboxylate (Int-54). MS (ESI) m/z 340 (M−+1).

Source