3-Nitrophenol → 4-[2-(3-Nitrophenoxy)ethyl]morpholine

A mixture of 3-nitrophenol (3.5 g, 25 mmol), N-(2-chloroethyl)morpholine hydrochloride (4.7 g, 25 mmol), and potassium carbonate (13.2 g, 125 mmol) in acetone (100 mL) was heated to reflux for 20 hours. The solvent was removed under vacuum. The residue was partitioned between water (150 mL) and ethyl acetate (150 mL) and the aqueous phase was extracted with ethyl acetate (100 mL). The combined organic layers were washed with water (3×100 mL) and extracted with dilute aqueous HCl (2×125 mL). These extracts were washed with CH2Cl2 (2×125 mL), made basic (NaOH) and extracted into ethyl acetate (3×75 mL). These organic extracts were washed with water (3×75 mL), dried (MgSO4), and evaporated, providing 4.4 g, in 70% yield; 1H NMR (CDCl3) δ 2.59 (t, J=4.7 Hz, 4H), 2.84 (t, J=5.6 Hz, 2H), 3.75 (t, J=4.7 Hz, 4H), 4.19 (t, J=5.6 Hz, 2H), 7.22-7.25 (m, 1H), 7.43 (t, J=8.1 Hz, 1H), 7.76 (t, J=2.3 Hz, 1H), 7.82-7.85 (m, 1H).

1. temperaturewas heated
2. temperatureto reflux for 20 hours
3. customThe solvent was removed under vacuum
4. customThe residue was partitioned between water (150 mL) and ethyl acetate (150 mL)
5. extractionthe aqueous phase was extracted with ethyl acetate (100 mL)
6. washThe combined organic layers were washed with water (3×100 mL)
7. extractionextracted with dilute aqueous HCl (2×125 mL)
8. washThese extracts were washed with CH2Cl2 (2×125 mL)
9. extractionextracted into ethyl acetate (3×75 mL)
10. washThese organic extracts were washed with water (3×75 mL)
11. dry with materialdried (MgSO4)
12. customevaporated
13. customproviding 4.4 g

ORD record

ord-d0997d4ad5d245a89a86a6a3ae5393e4

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481568B2