p-Bromochlorobenzene → HCID 66762742, compound

Temperature

-78 °C

To 1-bromo-4-chlorobenzene (424 mg, 2.21 mmol) in tetrahydrofuran (10 mL), at −78° C., was added n-butyllithium (1.0 mL of a 2.5 M solution in hexanes, 2.4 mmol) dropwise. After 0.5 h, a solution of the ketone (500 mg, 2.43 mmol) from Step B above in tetrahydrofuran (5 mL) was added dropwise. The reaction mixture was stirred at −78° C. for 0.5 h and then warmed to 0° C. After 1.5 h, the reaction mixture was quenched with saturated ammonium chloride (5 mL) and warmed to ambient temperature. The mixture was diluted with ethyl acetate (50 mL) and washed with saturated ammonium chloride (20 mL), water (20 mL), brine (20 mL), dried over sodium sulfate and concentrated in vacuo. Purification by silica gel chromatography (5% ethyl acetate/methylene chloride to 80% ethyl acetate/methylene chloride) gave 3-(4-chlorophenyl)-1-(3-methoxybenzyl)pyrrolidin-3-ol (250 mg, 35%) as a yellow oil: 1H NMR (CDCl3, 300 MHz) δ 7.50-7.42 (m, 2H), 7.34-7.29 (m, 2H), 7.27-7.22 (m, 1H), 6.96-6.91 (m, 2H), 6.83-6.80 (m, 1H), 3.82 (s, 3H), 3.57 (br s, 2H), 2.89-2.75 (m, 2H), 2.51-2.41 (m, 2H), 2.21-2.08 (m, 2H), 1.73-1.69 (m, 2H), 1.57 (s, 1H).

1. temperaturewarmed to 0° C
2. waitAfter 1.5 h
3. customthe reaction mixture was quenched with saturated ammonium chloride (5 mL)
4. temperaturewarmed to ambient temperature
5. additionThe mixture was diluted with ethyl acetate (50 mL)
6. washwashed with saturated ammonium chloride (20 mL), water (20 mL), brine (20 mL)
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated in vacuo
9. customPurification by silica gel chromatography (5% ethyl acetate/methylene chloride to 80% ethyl acetate/methylene chloride)

ORD record

ord-cfefaf1105aa488fbf81796749d2b5d3

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045468B2