Pyrrolidine → HCID 68751282, compound

HRID 624165Notes

Reaction equation

HRID 624165 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:17]O)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CS(Cl)(=O)=O.S([O-])(=O)(=O)C.[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1>ClCCl.O>[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:17][N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 22591344tert-butyl 5-(hydroxymethyl)-2,3-dihydro-1H-isoindole-2-carboxylate

Product 1

HCID 68751282HCID 68751282, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1.25 g 5-hydroxymethyl-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (5.01 mmol) in 14 ml dichloromethane was slowly added 0.781 ml methanesulfonyl chloride (10.03 mmol) at room temperature. Subsequently the mixture was heated for 4 hours at reflux. LCMS control indicted a near complete formation of the corresponding mesylate, which was not isolated. After cooling to room temperature, 1.244 ml pyrrolidine (15.04 mmol) were added and the mixture was stirred at room temperature overnight. The reaction was complete according to LCMS. Water was added to the reaction mixture, the acidic aqueous phase was extracted two times with dichloromethane, and the water phase was basified and extracted three times with ethyl acetate. The combined ethyl acetate solutions were extracted with brine, dried over Na2SO4, filtered, and the organic solvent was removed under reduced pressure to provide the title compound. The dichloromethane phase was extracted two times with diluted NaOH, once with brine and then dried over Na2SO4. Filtration and removal of the organic solvent under reduced pressure provided additional title compound. Both fractions were combined and used in the next step without further purification. LCMS: m/z 303.2 (M+H).

Workup

  1. customat room temperature
  2. temperatureSubsequently the mixture was heated for 4 hours
  3. temperatureat reflux
  4. customwas not isolated
  5. extractionthe acidic aqueous phase was extracted two times with dichloromethane
  6. extractionextracted three times with ethyl acetate
  7. extractionThe combined ethyl acetate solutions were extracted with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customthe organic solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-4fa35fa7be22420eb986305a5d0b5005
Source dataset
uspto-grants-2016_04
Patent number
US09302989B2

Reaction notes

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