Lithium Hydroxide → (R)-5-(2-(3-carboxy-5-fluorophenyl)-4,4-difluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylic acid

HRID 513046

Reaktionsgleichung

Reaktionsgleichung von HRID 513046
[C:1]([C:3]1[CH:4]=[C:5]([C@H:10]2[CH2:14][C:13]([F:16])([F:15])[CH2:12][N:11]2[C:17]2[CH:22]=[CH:21][N:20]3[N:23]=[CH:24][C:25]([C:26]([O:28]CC)=[O:27])=[C:19]3[CH:18]=2)[CH:6]=[C:7]([F:9])[CH:8]=1)#N.[Li+].[OH-:32].C1COCC1.C[OH:39].O>>[C:1]([C:3]1[CH:4]=[C:5]([C@H:10]2[CH2:14][C:13]([F:15])([F:16])[CH2:12][N:11]2[C:17]2[CH:22]=[CH:21][N:20]3[N:23]=[CH:24][C:25]([C:26]([OH:28])=[O:27])=[C:19]3[CH:18]=2)[CH:6]=[C:7]([F:9])[CH:8]=1)([OH:39])=[O:32]

Komponenten

4

Edukt 3

HCID 3939Lithium HydroxideHCID 21892291Methanol tetrahydrofuran waterHCID 60171438(R)-ethyl 5-(2-(3-cyano-5-fluorophenyl)-4,4-difluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylate

Produkt 1

HCID 68282203(R)-5-(2-(3-carboxy-5-fluorophenyl)-4,4-difluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylic acid

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A solution of (R)-ethyl 5-(2-(3-cyano-5-fluorophenyl)-4,4-difluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (X-8) (90 mg, 0.22 mmol) in THF:MeOH:H2O 3:2:1 (2.5 mL) was added LiOH (46 mg, 1.1 mmol) and stirred at 50° C. for 12 hours. The reaction was subsequently neutralized and concentrated to dryness. The crude product was purified by column chromatography on silica gel with DCM/MeOH gradient as eluant to yield (R)-5-(2-(3-carboxy-5-fluorophenyl)-4,4-difluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (I-52), which was immediately used in the next reaction. MS m/z 406.1 (M+1)+.

Aufarbeitung

  1. concentrationconcentrated to dryness
  2. customThe crude product was purified by column chromatography on silica gel with DCM/MeOH gradient as eluant

Quellen und Nachweise

ORD-Eintrag
ord-db544ffd171e4710bb3da5d9ee578eda
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102671B2

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