Sodium hydride → (R)-2-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2242879Notes

Reaction equation

HRID 2242879 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:18](=[O:19])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]2=[O:20])=[CH:6][CH:5]=1.[C:21]([O:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@@H:29]1[CH2:33]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:27])([CH3:24])([CH3:23])[CH3:22]>CN(C=O)C>[C:21]([O:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@@H:29]1[CH2:33][O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:18](=[O:19])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]2=[O:20])=[CH:8][CH:9]=1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 252281N-(4-Hydroxyphenyl)PhthalimideHCID 11760051(R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 58900146(R)-2-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 56.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 25 mL vial which contained a suspension of NaH (60% in mineral oil, 30 mg, 0.75 mmol) in DMF (3 mL) was added 2-(4-Hydroxy-phenyl)-isoindole-1,3-dione (105 mg, 0.5 mmol) at 0° C. The mixture was allowed to warm to rt and stir at rt for 30 min then cooled to 0° C. To this reaction mixture was added (R)-2-(toluene-4-sulfonyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (173 mg, 0.5 mmol) at 0° C. The resulting mixture was allowed to warm to rt and stir at rt for 30 min and then was heated to 90° C. and stirred at 90° C. for 16 h. After cooled to it, the mixture was poured into 150 mL ice-water solution and then was extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (3×50 mL), brine (30 mL) and dried over Na2SO4. After concentrated in vacuo, the residue was purified by a column chromatography on silica gel to yield the title product, (120 mg, 55%)

Workup

  1. temperaturethen cooled to 0° C
  2. temperatureto warm to rt
  3. stirringstir at rt for 30 min
  4. temperaturewas heated to 90° C.
  5. stirringstirred at 90° C. for 16 h
  6. temperatureAfter cooled to it
  7. extractionwas extracted with EtOAc (3×50 mL)
  8. washThe combined organic layers were washed with water (3×50 mL), brine (30 mL)
  9. dry with materialdried over Na2SO4
  10. concentrationAfter concentrated in vacuo
  11. customthe residue was purified by a column chromatography on silica gel

Sources & evidence

ORD record
ord-c2409853e5a8496d813f660553661de2
Source dataset
uspto-grants-2010_03
Patent number
US07674802B2

Reaction notes

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