Hydrochloric Acid → (S)-4-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid

HRID 407954Notes

Reaction equation

HRID 407954 reaction equation
[F:1][C:2]1[CH:27]=[C:26]([C:28]([O:30]C)=[O:29])[CH:25]=[CH:24][C:3]=1[O:4][C@H:5]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[C:6]1=[O:23].C[Si](C)(C)[O-].[K+].Cl>C1COCC1>[C:19]([O:18][C:16]([N:13]1[CH2:14][CH2:15][CH:10]([N:7]2[CH2:8][CH2:9][C@H:5]([O:4][C:3]3[CH:24]=[CH:25][C:26]([C:28]([OH:30])=[O:29])=[CH:27][C:2]=3[F:1])[C:6]2=[O:23])[CH2:11][CH2:12]1)=[O:17])([CH3:22])([CH3:20])[CH3:21]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 23668039Potassium trimethylsilanolate2×HCID 86688102(S)-tert-butyl 4-(3-(2-fluoro-4-(methoxycarbonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

Product 1

HCID 67469693(S)-4-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acidYield 95.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-tert-butyl 4-(3-(2-fluoro-4-(methoxycarbonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (900 mg, 2.06 mmol) was dissolved in THF (20 mL) and potassium trimethylsilanolate (529 mg, 4.12 mmol) was added and the reaction stirred at ambient temperature. After 2 hours, additional potassium trimethylsilanolate (529 mg, 4.12 mmol) was added and stirred for 3 hours, the reaction was poured into 1N HCl and extracted with EtOAc, dried over Na2SO4, filtered and concentrated to afford (S)-4-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid (834 mg, 1.97 mmol, 95.7% yield) as a white solid.

Workup

  1. stirringstirred for 3 hours
  2. extractionextracted with EtOAc
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7549cca080a041068350bb6ef330bc05
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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