1-Bromo-2-Chloroethane → HCID 767785, compound

To a solution of freshly prepared LDA (132 mL of n-butyl lithium, 2.5 M in hexane, 51 mL of diisopropylamine) in THF (anhydrous, 420 mL), DMPU (200 mL) at −78° C. was added a solution of A1 (60 g, 300 mmol) in THF (60 mL) at −78° C. After stirring for 40 min, 1-bromo-2-chloroethane (24.9 mL, 300 mmol) was added. After stirring for another 20 min at −78° C., the dry ice-acetone bath was removed and the reaction was slowly warmed up to rt. After stirring for an additional hour, the reaction mixture was cooled back to −78° C. and a solution of DMPU (200 mL) in THF (420 mL) was added. Another portion of freshly prepared LDA (120 mL of n-butyl lithium, 2.5 M in hexane, 47 mL of di-isopropylamine in THF (anhydrous, 420 ml)) was added into the reaction mixture by cannula at −78° C. After stirring for 1.5 h at −78° C., the dry ice-acetone bath was removed and the reaction was slowly warmed up to rt. After 5-6 h, the reaction was quenched with saturated aqueous ammonium chloride (300 mL) and concentrated. The residue was diluted with H2O (480 mL) and extracted with ethyl acetate/hexane (1:5 (v/v), 3×360 mL). The combined organic layers were washed with brine (500 mL) and then dried, filtered, and concentrated. The resulting crude product was purified by silica gel flash column chromatography (Hexanes/EtOAc=10/1 (v/v)) to provide A2 (35 g).

1. stirringAfter stirring for another 20 min at −78° C.
2. customthe dry ice-acetone bath was removed
3. stirringAfter stirring for an additional hour
4. temperaturethe reaction mixture was cooled back to −78° C.
5. additiona solution of DMPU (200 mL) in THF (420 mL) was added
6. additionAnother portion of freshly prepared LDA (120 mL of n-butyl lithium, 2.5 M in hexane, 47 mL of di-isopropylamine in THF (anhydrous, 420 ml)) was added into the reaction mixture by cannula at −78° C
7. stirringAfter stirring for 1.5 h at −78° C.
8. customthe dry ice-acetone bath was removed
9. temperaturethe reaction was slowly warmed up to rt
10. waitAfter 5-6 h
11. customthe reaction was quenched with saturated aqueous ammonium chloride (300 mL)
12. concentrationconcentrated
13. additionThe residue was diluted with H2O (480 mL)
14. extractionextracted with ethyl acetate/hexane (1:5 (v/v), 3×360 mL)
15. washThe combined organic layers were washed with brine (500 mL)
16. customdried
17. filtrationfiltered
18. concentrationconcentrated
19. customThe resulting crude product was purified by silica gel flash column chromatography (Hexanes/EtOAc=10/1 (v/v))

ORD record

ord-fa0db5913f374c8cb5bcf8c8ad335a64

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09120779B2