Dimethylformamide → 5-Ethoxy-2-fluorobenzaldehyde

Temperature

-40 °C

To a solution of 1-ethoxy-4-fluorobenzene (1.1 g, 7.9 mmol) and pentamethyl diethylene triamine (2 mL) in anhydrous THF (6 mL) was added BuLi dropwise (1.38 M, 5.98 mL, 8.3 mmol) at −78° C. After addition, the reaction mixture was warmed up to −40° C. and stirred for 30 min, the reaction mixture was then cooled to −78° C. and DMF (0.7 mL) was added. The solution was warmed to rt, and stirred for 1 h. The reaction mixture was then partitioned between EtOAc and sat. NH4Cl, the organic layer was dried over (Na2SO4), filtered and concentrated. The residue was subjected to chromatographic purification (0-10% EtOAc/hexanes gradient), 600 mg (55%) of Intermediate 53.1 was obtained. 1H NMR (CDCl3) δ 1.40 (t, 3H), 4.08 (q, 2H), 6.81 (m, 1H), 7.15 (m, 1H), 7.29 (m, 1H), 10.33 (s, 1H).

1. additionAfter addition
2. temperaturethe reaction mixture was then cooled to −78° C.
3. temperatureThe solution was warmed to rt
4. stirringstirred for 1 h
5. customThe reaction mixture was then partitioned between EtOAc and sat. NH4Cl
6. dry with materialthe organic layer was dried over (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was subjected to chromatographic purification (0-10% EtOAc/hexanes gradient)

ORD record

ord-eb55b0b4a971477b89bb4b8cb59af4a6

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07576098B2