Lithium Hydroxide → (S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinic acid

HRID 408012Notes

Reaction equation

HRID 408012 reaction equation
[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:22][CH2:21][C@H:20]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][C:25]=4[F:34])[C:19]3=[O:35])[CH2:14][CH2:13]2)=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9]C)=[O:8].[Li+].[OH-]>C1COCC1>[Cl:1][C:2]1[C:3]([N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[CH2:22][CH2:21][C@H:20]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:26][C:25]=4[F:34])[C:19]3=[O:35])[CH2:16][CH2:17]2)=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([OH:9])=[O:8]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67469943(S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinate

Product 1

HCID 86688119(S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinic acidYield 82.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinate (Example 156, Step A; 0.50 g, 0.95 mmol) in THF (20 mL) was added a 3 M solution of LiOH (3 mL) and the reaction was stirred overnight at ambient temperature. The THF was removed with a stream of nitrogen. The aqueous layer was acidified to pH 1 by the addition of 1 N HCl. The solids that formed were filtered, washed with water and dried under vacuum to give (S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinic acid (0.40 g, 82% yield).

Workup

  1. customThe THF was removed with a stream of nitrogen
  2. additionThe aqueous layer was acidified to pH 1 by the addition of 1 N HCl
  3. customThe solids that formed
  4. filtrationwere filtered
  5. washwashed with water
  6. customdried under vacuum

Sources & evidence

ORD record
ord-a826d26f5e914be68fc9154c2534caef
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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