Pyridine → Carbonic acid 3'-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl ester methyl ester

A solution of (3′-Chloro-2-fluoro-6-methoxy-biphenyl-3-yl)-methanol (I-32, 3.00 g, 11.3 mmol) in pyridine (2.31 g, 29.3 mmol) and tetrahydrofuran (40 mL) was cooled to 0° C. in an ice water bath. The reaction vessel was purged with nitrogen and methyl chloroformate (2.34 g, 24.8 mmol) was added. The ice bath was removed and the reaction was stirred at room temperature overnight. The white suspension was adjusted to pH 2 by addition of 1 N aqueous hydrochloric acid (˜25 mL) and the yellow biphasic solution was diluted with dichloromethane (200 mL) and water (150 mL). The layers were separated, and the aqueous layer was extracted with dichloromethane (2×100 mL). The dichloromethane extracts were combined, washed with water (2×200 mL) and brine (200 mL), dried over sodium sulfate, filtered, and the solvent removed under vacuum to give I-145 (3.84 g, quantitative yield).

1. additionwas added
2. customThe ice bath was removed
3. additionThe white suspension was adjusted to pH 2 by addition of 1 N aqueous hydrochloric acid (˜25 mL)
4. additionthe yellow biphasic solution was diluted with dichloromethane (200 mL) and water (150 mL)
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with dichloromethane (2×100 mL)
7. washwashed with water (2×200 mL) and brine (200 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. customthe solvent removed under vacuum
11. customto give I-145 (3.84 g, quantitative yield)

ORD record

ord-a4ee9dcfcf8a4706a9257052bd605d51

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791267B2