Isopropanol → (3-Amino-4-fluorophenyl)methanol

A flask equipped with overhead stirrer was charged with 4-fluoro-3-nitrobenzyl alcohol (20 g, 0.117 mol) and 200 mL of 5:1 isopropanol: water. Ammonium chloride (62 g, 1.17 mol) was added followed by iron filings (65 g, .17 mol). The mixture was stirred at 70 C for 1.5 H when it was shown to be complete by LC-MS. The liquid was decanted and the solids were washed with additional isopropanol:water. The isopropanol was removed and the residue was diluted with 0.5 N HCl and was extracted with ethyl acetate. The aqueous layer was brought to pH 12-14 with 2.5 N NaOH and was extracted with ethyl acetate. The organic layer was dried with anhydrous Na2SO4 and concentrated in vacuo. 3-Amino-4-fluorophenyl methanol was isolated as a brown solid (4.5 g, 27%) and was used without further purification. LC/MS, tr=2.40 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 142 (M+H). ES-HRMS m/z 142.0692 (M+H calcd for C7H8FNO requires 142.0663). Step 2 Preparation of 1-[2-fluoro-5-(hydroxymethyl)phenyl]-4-hydroxy-6-methylpyridin-2(1H)-one

1. customA flask equipped with overhead stirrer
2. customThe liquid was decanted
3. washthe solids were washed with additional isopropanol
4. customThe isopropanol was removed
5. additionthe residue was diluted with 0.5 N HCl
6. extractionwas extracted with ethyl acetate
7. extractionwas extracted with ethyl acetate
8. dry with materialThe organic layer was dried with anhydrous Na2SO4
9. concentrationconcentrated in vacuo

ORD record

ord-b316dffefae147a49ccabbb354215561

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067540B2