3-Bromo-2-fluorobenzaldehyde → (3-Bromo-2-fluorophenyl)(pyridin-2-yl)methanol

Temperatur

-78 °C

To a solution of 3-bromo-2-fluorobenzaldehyde (0.250 g, 1.231 mmol) in THF (5.35 mL) cooled to −78° C. was added pyridin-2-ylmagnesium bromide (5.91 mL, 1.478 mmol). The reaction mixture was maintained at −78° C. for at least 1 hr, then allowed to warm to room temperature slowly over 2 hr. The reaction quenched with a saturated aqueous solution of NH4Cl. The reaction mixture was diluted with CH2Cl2. Layers were separated. The aqueous phase was extracted with CH2Cl2 (2×). The organics were combined, dried over Na2SO4, filtered, and concentrated to afford a yellow residue. The crude material was dissolved in a minimal amount CH2Cl2 and chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (40 g column, 40 mL/min, 1-40% EtOAc in hexanes over 25 min, tr=16 min) gave the title compound (78 mg, 0.276 mmol, 22.45% yield) as a yellow residue.

1. temperatureto warm to room temperature slowly over 2 hr
2. customThe reaction quenched with a saturated aqueous solution of NH4Cl
3. additionThe reaction mixture was diluted with CH2Cl2
4. customLayers were separated
5. extractionThe aqueous phase was extracted with CH2Cl2 (2×)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a yellow residue
10. customchromatographed
11. customPurification of the crude material by silica gel chromatography
12. customan ISCO machine (40 g column, 40 mL/min, 1-40% EtOAc in hexanes over 25 min, tr=16 min)

ORD-Eintrag

ord-35f35717dceb4b6ba0856ae78e056dcc

Quelldatensatz

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09242967B2