5-Fluoroindole-2-carboxylic acid → 4-Benzyloxy-3-hydroxymethylaniline

A mixture of an amine (see Table 1 below for amines) (0.1 mmol), an acid (5-fluoroindole-2-carboxylic acid or 5-fluoro-3-phenylindole-2-carboxylic acid) (0.1 mmol as 0.1 mL of 1M solution in THF), and DIEA (0.05 mL, 0.3 mmol) in 0.4 mL of CH2Cl2-THF (3:1) was cooled to 0° C. PyBrOP (0.1 mmol) was added. The reaction mixture was shaken using an orbital shaker at 0° C. for 30 minutes then at room temperature for 48 hours (0.1 mL THF and 0.2 mL CH2Cl2 were added after 24 hours). EtOAc was added to the mixture and the organic solution was washed with 1M HCl (2×1 mL), brine (1 mL) NaHCO3 (2×1 mL), and brine (1 mL). The organic layer was passed through a silica gel cartridge containing a top layer of anhydrous MgSO4 and moistened with hexane. The product amide was eluted with hexane (1×1 mL), hexane-EtOAc 2:1 (3×1 mL), hexane-EtOAc 1:1 (2×2 mL), and hexane-EtOAc 1:2 (1×2 mL). The fraction(s) containing pure product was identified by TLC (EtOAc-hexane 1:1 and EtOAc-hexane 1:2 in the case of 5-fluoro-3-phenylindole-2-carboxylic acid amide derivatives). The compounds were characterized by 1H NMR.

1. customat 0° C.
2. customfor 30 minutes
3. washthe organic solution was washed with 1M HCl (2×1 mL), brine (1 mL) NaHCO3 (2×1 mL), and brine (1 mL)
4. additioncontaining a top layer of anhydrous MgSO4
5. washThe product amide was eluted with hexane (1×1 mL), hexane-EtOAc 2:1 (3×1 mL), hexane-EtOAc 1:1 (2×2 mL), and hexane-EtOAc 1:2 (1×2 mL)
6. additionThe fraction(s) containing pure product

ORD 기록

ord-7ae89fc2f3e747d08ebce64e7c2e1931

출처 데이터셋

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07427608B2