1-Oxo-2,3-Dihydro-1H-Indene-4-Carbonitrile → HCID 14515308, 화합물

To a 3-neck flask with an internal thermometer and an addition funnel was added (R)-(+)-2-methyl-CBS-oxazaborolidine solution in toluene (3.0 mL) and borane-dimethylsulfide (300 μL). The reaction was stirred at room temperature for 10 min then diluted with DCM (25 mL). Borane-dimethylsulfide (6.0 mL) was added and, after stirring for 5 min, the reaction was cooled to −20° C. 1-oxo-2,3-dihydro-1H-indene-4-carbonitrile INT-1 (4.7 g, 30 mmol) in DCM (25 mL) was added dropwise by addition funnel over 20 min while maintaining the reaction at −20±5° C. The reaction was stirred for 1 h then quenched by the dropwise addition of MeOH (20 mL). After hydrogen evolution ceased, MeOH (30 mL) was added and removed by heating at atmospheric pressure. MeOH (50 mL) was added in two and removed by heating twice. All the solvent was evaporated to give a solid which was recrystallized from EA (9 mL) and hexane (22 mL). The compound was filtered and washed with 5:1 hexane/EA (30 mL) to provide 3.73 g (78%) of (S)-1-hydroxy-2,3-dihydro-1H-indene-4-carbonitrile INT-2 as a white powder. LCMS-ESI (m/z) calculated for C10H9NO: 159.1; found 160.1 [M+H]+, tR=2.39 min. 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J=7.6 Hz, 1H), 7.53 (d, J=7.6 Hz, 1H), 7.32 (t, J=7.6 Hz, 1H), 5.28 (d, J=4.1 Hz, 1H), 3.23 (ddd, J=17.0, 8.7, 4.4 Hz, 1H), 3.04-2.90 (m, 1H), 2.64-2.51 (m, 1H), 2.00 (dddd, J=13.4, 8.7, 7.1, 5.7 Hz, 1H), 1.91 (d, J=5.4 Hz, 1H). Chiral HPLC: (S)-1-hydroxy-2,3-dihydro-1H-indene-4-carbonitrile was eluted in 20% IPA in hexane: >99.9% ee, tR=7.42 min. The (R)-enantiomer was obtained in an analogous fashion using (S)-(−)-2-methyl-CBS-oxazaborolidine. tR for (R)-enantiomer=6.79 min.

1. stirringafter stirring for 5 min
2. temperaturethe reaction was cooled to −20° C
3. temperaturewhile maintaining
4. customthe reaction at −20±5° C
5. stirringThe reaction was stirred for 1 h
6. customthen quenched by the dropwise addition of MeOH (20 mL)
7. additionMeOH (30 mL) was added
8. customremoved
9. temperatureby heating at atmospheric pressure
10. additionMeOH (50 mL) was added in two
11. customremoved
12. temperatureby heating twice
13. customAll the solvent was evaporated
14. customto give a solid which
15. customwas recrystallized from EA (9 mL) and hexane (22 mL)
16. filtrationThe compound was filtered
17. washwashed with 5:1 hexane/EA (30 mL)

ORD 기록

ord-dad36ac4315942698507e4b6b0199964

출처 데이터셋

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08362048B2