Phthalimide → (2R)-tert-butyl 2-(2-(3-chloro-4-fluorophenyl)-2-(1,3-dioxoisoindolin-2-yl)ethyl)pyrrolidine-1-carboxylate

HRID 2279589Notes

Reaction equation

HRID 2279589 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9](O)[CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:5]=[CH:6][C:7]=1[F:8].[C:24]1(=[O:34])[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26](=[O:33])[NH:25]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([N:25]2[C:26](=[O:33])[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:24]2=[O:34])[CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 86705571(2R)-tert-butyl 2-(2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl)pyrrolidine-1-carboxylate

Product 1

HCID 86705572(2R)-tert-butyl 2-(2-(3-chloro-4-fluorophenyl)-2-(1,3-dioxoisoindolin-2-yl)ethyl)pyrrolidine-1-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 301 (0.0754 g, 0.219 mmol), isoindoline-1,3-dione (0.0387 g, 0.263 mmol) and PPh3 (0.127 g, 0.482 mmol) in THF cooled to 0° C. was added DEAD (0.0760 mL, 0.482 mmol) and the reaction warmed to RT and stirred overnight. 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 an oil. The crude oil was purified by SiO2 chromatography to afford 0.0507 g (49%) of (2R)-tert-butyl 2-(2-(3-chloro-4-fluorophenyl)-2-(1,3-dioxoisoindolin-2-yl)ethyl)pyrrolidine-1-carboxylate (303) 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 to an oil
  7. customThe crude oil was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-72246da9a3f543bb8045bf7f7585e988
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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