Lithium Hydroxide → (3S,4R)-4-(2,4-Difluorophenyl)-1-isopropylpyrrolidine-3-carboxylic acid

HRID 1992678Notes

Reaction equation

HRID 1992678 reaction equation
[OH-].[Li+].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C@@H:11]1[CH2:15][N:14]([CH:16]([CH3:18])[CH3:17])[CH2:13][C@H:12]1[C:19]([O:21]C)=[O:20]>O1CCCC1>[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C@@H:11]1[CH2:15][N:14]([CH:16]([CH3:17])[CH3:18])[CH2:13][C@H:12]1[C:19]([OH:21])=[O:20]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 59130981Methyl (3S,4R)-4-(2,4-difluorophenyl)-1-isopropylpyrrolidine-3-carboxylate

Product 1

HCID 59131011(3S,4R)-4-(2,4-Difluorophenyl)-1-isopropylpyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide (171 mg, 7.14 mmol) was added to a solution of methyl (3S,4R)-4-(2,4-difluorophenyl)-1-isopropylpyrrolidine-3-carboxylate, from preparation 32 (1.01 g, 3.59 mmol) in tetrahydrofuran (10 mL) at room temperature. The reaction mixture was stirred for 3 hours and the solvent was removed in vacuo. The residue was dissolved in water (20 mL) and washed with ethyl acetate (2×20 mL). The phases were separated and the aqueous phase was acidified with 2M aqueous hydrochloric acid solution (3.59 mL) and extracted with ethyl acetate (20 mL). The organic extracts were combined, dried over magnesium sulfate and concentrated in vacuo to afford the desired product as a foam, 686 mg (71%).

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in water (20 mL)
  3. washwashed with ethyl acetate (2×20 mL)
  4. customThe phases were separated
  5. extractionextracted with ethyl acetate (20 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e9392cc5a082401a80b4d91c01ba89b8
Source dataset
uspto-grants-2010_01
Patent number
US07649002B2

Reaction notes

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