Aluminium lithium hydride → (3-Amino-2-fluorophenyl)methanol

3-amino-2-fluorobenzoic acid (APIN, 250 mg, 1.612 mmol) was dissolved in 10 mL of anhydrous THF under N2 atmosphere. Solution was cooled at 0° C. in an ice-water bath. LiAlH4 (FLUKA, 183 mg, 4.83 mmol) was added. Reaction was stirred under nitrogen at room temperature. After 2 h one equivalent of LiAlH4 (FLUKA, 61 mg, 1.62 mmol) was added to the mixture and reaction was stirred at room temperature overnight. Another equivalent of LiAlH4 (FLUKA, 61 mg, 1.62 mmol) was added. After 5 h The reaction mixture was quenched by adding MeOH. Solvent was evaporated to obtain an orange syrup that was dissolved in EtOAc and partitioned with saturated NaHCO3 (aqueous) (10 mL of saturated solution+15 mL of distilled water). Aqueous phase was extracted with EtOAc, organic layers were combined and dried with MgSO4 (anh), filtered off and concentrated. Crude was purified using silica gel cartridge with linear gradient 0-85% DCM/MeOH to yield the title compound (114 mg, 0.808 mmol, 50.1% yield) as yellow syrup. 1H NMR (300 MHz, DMSO-d6) δ ppm: 6.50-6.85 (m, 3H), 4.95-5.08 (m, 3H), 4.44 (d, 2H).

1. customReaction
2. stirringwas stirred at room temperature overnight
3. customAfter 5 h The reaction mixture was quenched
4. additionby adding MeOH
5. customSolvent was evaporated
6. customto obtain an orange syrup that
7. custompartitioned with saturated NaHCO3 (aqueous) (10 mL of saturated solution+15 mL of distilled water)
8. extractionAqueous phase was extracted with EtOAc, organic layers
9. dry with materialdried with MgSO4 (anh)
10. filtrationfiltered off
11. concentrationconcentrated
12. customCrude was purified

ORD-Eintrag

ord-970e1aba485d4c99b3702526307d880f

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08524750B2