Lithium Carbonate → 2-chloro-4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]-3-methylbenzonitrile

HRID 2046629Notes

Reaction equation

HRID 2046629 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][NH:4][C@H:3]1[CH3:7].[Cl:8][C:9]1[C:16]([CH3:17])=[C:15](F)[CH:14]=[CH:13][C:10]=1[C:11]#[N:12].C(=O)([O-])[O-].[Li+].[Li+]>CS(C)=O>[Cl:8][C:9]1[C:16]([CH3:17])=[C:15]([N:4]2[CH2:5][CH2:6][C@H:2]([OH:1])[C@@H:3]2[CH3:7])[CH:14]=[CH:13][C:10]=1[C:11]#[N:12]

Participants

5

Reactant 3

HCID 11125Lithium CarbonateHCID 445509712-Chloro-4-fluoro-3-methylbenzonitrileHCID 54198127HCID 54198127, compound

Product 1

HCID 593705002-chloro-4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]-3-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2S,3S)-3-hydroxy-2-methylpyrrolidine, 2-chloro-4-fluoro-3-methylbenzonitrile (424 mg), lithium carbonate (370 mg) and DMSO (12.5 ml) was stirred at 100° C. for 2 hr. The reaction mixture was cooled and partitioned between water and ethyl acetate. The organic layer was washed with water, dried (sodium sulfate), and concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate-hexane), and crystallized from ethyl acetate-hexane to give the title compound (114 mg) as crystals.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between water and ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialdried (sodium sulfate)
  5. concentrationconcentrated
  6. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate-hexane)
  7. customcrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-53884cf2466646b4b4939094bdf7f4a5
Source dataset
uspto-grants-2013_11
Patent number
US08592452B2

Reaction notes

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