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

HRID 2046625Notes

Reaction equation

HRID 2046625 reaction equation
[OH:1][C:2]([C@H:5]1[CH2:9][CH2:8][NH:7][C@H:6]1[CH3:10])([CH3:4])[CH3:3].[Cl:11][C:12]1[C:19]([CH3:20])=[C:18](F)[CH:17]=[CH:16][C:13]=1[C:14]#[N:15].C(=O)([O-])[O-].[Li+].[Li+]>CS(C)=O>[Cl:11][C:12]1[C:19]([CH3:20])=[C:18]([N:7]2[CH2:8][CH2:9][C@H:5]([C:2]([OH:1])([CH3:4])[CH3:3])[C@@H:6]2[CH3:10])[CH:17]=[CH:16][C:13]=1[C:14]#[N:15]

Participants

5

Reactant 3

HCID 11125Lithium CarbonateHCID 445509712-Chloro-4-fluoro-3-methylbenzonitrileHCID 55299039(2S,3S)-3-(1-hydroxy-1-methylethyl)-2-methylpyrrolidine

Product 1

HCID 159402542-chloro-4-[(2S,3S)-3-(1-hydroxy-1-methylethyl)-2-methylpyrrolidin-1-yl]-3-methylbenzonitrileYield 16.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of compound 1 (1.56 g), 2-chloro-4-fluoro-3-methylbenzonitrile (1.27 g), lithium carbonate (1.16 g) and DMSO (37.5 ml) was stirred at 100° C. for 1 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 (357 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-03846190ece646a489999390347edb5b
Source dataset
uspto-grants-2013_11
Patent number
US08592452B2

Reaction notes

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