1,1,1-Trifluoro-2-propanol → Methyl 5-chloro-6-(2,2,2-trifluoro-1-methylethoxy)nicotinate

Temperature

0 °C

To a solution of 630 mg (3.06 mmol) of methyl 5,6-dichloronicotinate (from Step A) and 349 μL (3.06 mmol) of 1,1,1-trifluoro-2-propanol in 10 mL of THF at −78° C. was added 3.1 mL (3.06 mmol) of sodium bis(trimethylsilyl)amide (1.0 M in THF). After stirring at −78° C. for 30 min and at 0° C. for 5 h, the reaction was quenched by adding 10 mL of saturated NH4Cl. The mixture was poured into brine and extracted with CH2Cl2 (3×20 mL). Organic layers were combined, dried over MgSO4, and concentrated. Chromatography on a Biotage 40M cartridge using 3:97 v/v Et2O/hexanes as the eluant gave 627 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.56 (d, J=6.4, 3H), 3.93 (s, 3H), 5.86 (m, 1H), 8.27 (d, J=2.1, 1H), 8.67 (d, J=2.0, 1H).

1. customthe reaction was quenched
2. additionby adding 10 mL of saturated NH4Cl
3. additionThe mixture was poured into brine
4. extractionextracted with CH2Cl2 (3×20 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated

ORD record

ord-ac8018d2b2df49f5b25c580b43830a78

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07605171B2