1-Indanone, 4-bromo- → (S)-4-broMo-2,3-dihydro-1H-inden-1-ol

To a 100 mL 3-neck flask equipped with an internal thermometer and an addition funnel was added (R)-(+)-2-methyl-CBS-oxazaborolidine (1.6 ml, 1M solution in toluene) and borane-dimethylsulfide (150 uL) under N2. The reaction was stirred at room temperature for 10 min then diluted with DCM (10 mL). Borane-dimethylsulfide (6.0 mL) was added and the reaction cooled to −20° C. A solution of 4-Bromo-2,3-dihydro-1H-inden-1-one (2.5 g, 11.8 mmol) in DCM (10 mL) was added dropwise over 20 min while maintaining the reaction temperature at −20±5° C. The reaction was stirred for 2 h after the addition was complete, then quenched by the dropwise addition of MeOH (10 mL). The reaction mixture was diluted with MeOH (20 mL) and the solvent distilled at atmospheric pressure. MeOH (30 mL) was added in two portions and the distillation was repeated twice. All the solvent was evaporated to give a solid which was purified by silica gel column chromatography (EA/hexanes) and recrystallization from 5:1 hexane/EA (30 mL) to provide 1.56 g (62%) of (S)-4-bromo-2,3-dihydro-1H-inden-1-ol as a white powder IND INT-1. LCMS-ESI (m/z) calculated for C9H9BrO: 213.1; found 196.9 [M-OH]+, tR=3.06 min. 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J=7.9 Hz, 1H), 7.33 (d, J=7.5 Hz, 1H), 7.10 (t, J=7.7 Hz, 1H), 5.29 (dd, J=12.6, 6.9 Hz, 1H), 3.05 (ddd, J=16.6, 8.7, 4.6 Hz, 1H), 2.87-2.71 (m, 1H), 2.50 (dddd, J=13.2, 8.4, 7.0, 4.6 Hz, 1H), 1.94 (dddd, J=13.5, 8.8, 6.6, 5.5 Hz, 1H), 1.80 (d, J=7.1 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 146.82, 143.50, 131.24, 128.58, 123.21, 120.25, 76.83, 34.69, 31.19. Chiral HPLC: (S)-4-bromo-2,3-dihydro-1H-inden-1-ol was eluted using 10% IPA in hexanes: >99.9% % ee, tR=6.27 min.

1. customTo a 100 mL 3-neck flask equipped with an internal thermometer and an addition funnel
2. temperaturethe reaction cooled to −20° C
3. temperaturewhile maintaining the reaction temperature at −20±5° C
4. stirringThe reaction was stirred for 2 h
5. additionafter the addition
6. customquenched by the dropwise addition of MeOH (10 mL)
7. additionThe reaction mixture was diluted with MeOH (20 mL)
8. distillationthe solvent distilled at atmospheric pressure
9. additionMeOH (30 mL) was added in two portions
10. distillationthe distillation
11. customAll the solvent was evaporated
12. customto give a solid which
13. customwas purified by silica gel column chromatography (EA/hexanes) and recrystallization from 5:1 hexane/EA (30 mL)

ORD record

ord-8480a64e394e4dd980c693c311c6e1d7

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507538B2