Hydrochloric Acid → (2-Chloro-3-Fluoropyridin-4-Yl)Methanol

HRID 1527462Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1527462
C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl:13][C:14]1[C:15]([F:23])=[C:16]([CH:20]=[CH:21][N:22]=1)[C:17](O)=[O:18].[BH4-].[Na+].Cl>C1COCC1.O>[Cl:13][C:14]1[C:15]([F:23])=[C:16]([CH2:17][OH:18])[CH:20]=[CH:21][N:22]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 27828122-Chloro-3-fluoropyridine-4-carboxylic acidHCID 4311764Sodium borohydride

Produkt 1

HCID 54759140(2-Chloro-3-Fluoropyridin-4-Yl)Methanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Carbonyldiimidazole (1.80 g, 11.1 mmol) was added to a solution of 2-chloro-3-fluoro-isonicotinic acid (1.3 g, 7.41 mmol) in THF (21.2 mL). The reaction mixture was stirred at RT overnight and was then added to a cold (0° C.) solution of NaBH4 (1.40 g, 37 mmol) in water (52.9 mL). The mixture was stirred for 10 min at 0° C., and 1M HCl was then added carefully to quench the reaction (caution: H2 evolving). Volatiles were removed via rotary evaporation and the residue was dissolved in saturated aqueous NaHCO3. The mixture was extracted repeatedly with CH2Cl2, the combined organics were dried (phase separator) and concentrated in vaccuo. Purification by flash column chromatography on silica gel (eluent gradient: c-hexane/EtOAc 4:1 to 2:1) afforded the title compound as a white solid. TLC, Rf (c-hexane/EtOAc 1:1)=0.37; MS (LC/MS): 162.0 [M+H]+; tR (HPLC conditions b): 1.60 min.

Aufarbeitung

  1. stirringThe mixture was stirred for 10 min at 0° C.
  2. customto quench
  3. customthe reaction (caution: H2 evolving)
  4. customVolatiles were removed via rotary evaporation
  5. dissolutionthe residue was dissolved in saturated aqueous NaHCO3
  6. extractionThe mixture was extracted repeatedly with CH2Cl2
  7. customthe combined organics were dried (phase separator)
  8. concentrationconcentrated in vaccuo
  9. customPurification by flash column chromatography on silica gel (eluent gradient: c-hexane/EtOAc 4:1 to 2:1)

Quellen und Nachweise

ORD-Eintrag
ord-173893a6dfd447d29617f0a1a9a409fb
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09085555B2

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