1-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl ester → tert-butyl 5-(7-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-2,3-dihydro-1H-pyrrole-1-carboxylate

HRID 1476768Notes

Reaction equation

HRID 1476768 reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[C:16]2[O:15][CH2:14][CH2:13][O:12][C:11]=2[CH:10]=[C:9]([F:17])[CH:8]=1.O=[C:19]1[CH2:23][CH2:22][CH2:21][N:20]1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>C1COCC1>[F:17][C:9]1[CH:8]=[C:7]([C:19]2[N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21][CH2:22][CH:23]=2)[C:16]2[O:15][CH2:14][CH2:13][O:12][C:11]=2[CH:10]=1

Participants

5

Reactant 3

HCID 3790001-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl esterHCID 896359545-Bromo-7-fluoro-2,3-dihydrobenzo[b][1,4]dioxineHCID 178418918HCID 178418918, compound

Product 1

HCID 89618649tert-butyl 5-(7-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-2,3-dihydro-1H-pyrrole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
5 °C

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).

Workup

  1. temperatureThe reaction mixture was cooled again to −45° C.
  2. temperaturemaintaining the temperature at −45° C
  3. temperatureThe reaction mixture was warmed to 25° C.
  4. customquenched with saturated NH4Cl solution (100 mL)
  5. extractionThe reaction mixture was extracted with ethyl acetate (3×30 mL)
  6. dry with materialthe organic layer was dried over anhydrous sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. custompurified by column chromatography (using silica gel and 20% ethyl acetate Hexane as eluent)

Sources & evidence

ORD record
ord-0d29cc54400143918288132dde83ca7b
Source dataset
uspto-grants-2016_08
Patent number
US09402833B2

Reaction notes

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