Lithium Hydroxide → (S)-4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid

HRID 408006Notes

Reaction equation

HRID 408006 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([F:32])[C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][C@H:16]([O:19][C:20]4[CH:29]=[CH:28][C:23]([C:24]([O:26]C)=[O:25])=[CH:22][C:21]=4[F:30])[C:15]3=[O:31])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[OH-].[Li+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([F:32])[C:5]([N:8]2[CH2:9][CH2:10][CH:11]([N:14]3[CH2:18][CH2:17][C@H:16]([O:19][C:20]4[CH:29]=[CH:28][C:23]([C:24]([OH:26])=[O:25])=[CH:22][C:21]=4[F:30])[C:15]3=[O:31])[CH2:12][CH2:13]2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 67469768HCID 67469768, compound

Product 1

HCID 67469835(S)-4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acidYield 90.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-methyl 4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoate (1.5 g, 3.2 mmol) in THF (30 mL) was added 3 N lithium hydroxide (4.3 mL, 13 mmol) and the reaction was stirred overnight at ambient temperature. Additional 3 N LiOH (4.3 mL, 13 mmol) was added, and the reaction was stirred for an additional 3 hours. The THF was removed with a stream of nitrogen. The aqueous layer was acidified by addition of HCl (1 N) and the solid that formed was filtered and washed with water. The solid was dried under vacuum to yield (S)-4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid (1.3 g, 2.9 mmol, 89% yield).

Workup

  1. stirringthe reaction was stirred for an additional 3 hours
  2. customThe THF was removed with a stream of nitrogen
  3. additionThe aqueous layer was acidified by addition of HCl (1 N)
  4. customthe solid that formed
  5. filtrationwas filtered
  6. washwashed with water
  7. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-5ada155eb0b24d1f8d9e59cd4e3b4c78
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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