Benzyl Chloride → 4-Benzyloxy-3-chloroaniline

To 4-amino-2-chlorophenol (7.23 g, 50 mmol) dissolved in acetone (250 mL), was added potassium carbonate (6.94 g, 50 mmol), followed by the addition of benzyl chloride (5.8 mL, 50 mmol), tetrabutylammonium bromide (TBAB) (1.66 g, 5 mmol), and potassium hydroxide (2.84 g, 50 mmol). The reaction mixture was allowed to stir at reflux overnight under nitrogen. The reaction mixture was extracted three times using dichloromethane; the combined organic layers were washed with brine and dried over potassium carbonate. The sample was concentrated and the resulting oil was dried overnight under vacuum. The material was purified by silica gel flash column chromatography eluting with 50:50 v:v hexanes:ethyl acetate and the collected fractions were concentrated in vacuo to give E1 (9.3 g, 80%); mp 54° C.; HPLC: Inertsil ODS 3V C18, 40:30:30 [KH2PO4 (0.01 M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 14.8 min, 98.7% purity; MS (TOF ES+) m/z 234 (M+H, 100).

1. temperatureat reflux overnight under nitrogen
2. extractionThe reaction mixture was extracted three times
3. washthe combined organic layers were washed with brine
4. dry with materialdried over potassium carbonate
5. concentrationThe sample was concentrated
6. customthe resulting oil was dried overnight under vacuum
7. customThe material was purified by silica gel flash column chromatography
8. washeluting with 50:50 v
9. concentrationv hexanes:ethyl acetate and the collected fractions were concentrated in vacuo

ORD record

ord-a61031691c0f40c59e6799778e7a6f51

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07332490B2