Triethylamine → Trans-10a-[(4-chlorophenyl)sulfonyl]-1,4-difluoro-6a, 9,10,10a-tetrahydrospiro[6H-dibenzo[b,d]pyran-8(7H), 2'-[1,3]dioxolane]

3-[2-(2-Benzyloxy-ethyl)-[1,3]dioxolan-2-ylmethyl]-4-(4-chloro-benzenesulfonyl)-5,8-difluoro-chroman (6.3 g, 11.2 mmole) was dissolved in 200 ml EtOAc and Pd(OH)2 (0.5 g) was added. Hydrogen was introduced via a balloon. The reaction was stirred at room temperature for 45 minutes. The catalyst was filtered and the filtrate was concentrated. The residue was dissolved in 200 ml DCM and MsCl (1.4 g, 12 mmole) and NEt3 (1.7 g, 17 mmole) were added. The mixture was stirred at room temperature for ten minutes. 200 ml water and 100 ml DCM were added. The organic layer was washed with 1N HCl (100 ml), water (100 ml), brine (100 ml), dried over Na2SO4 and concentrated. The residue was dissolved in 200 ml THF and KOt-Bu (1M in THF, 14 ml) was added. The mixture was stirred at room temperature for twenty minutes. 200 ml water and 200 ml EtOAc were added. The organic layer washed with brine (200 ml), dried over Na2SO4 and concentrated. The product was purified by column (EtOAc/hexane from 0/100 to 25/75 in 45 minutes). Yield: 3.1 g, 61%. 1H NMR (CDCl3 400 MHz δ 7.61 (d, J=8.8 Hz, 2H), 7.49 (d, J=8.8 Hz, 2H), 7.07 (m, 1H), 6.42 (m, 1H), 5.23 (dd, J=11.7 and 2.9 Hz, 1H), 4.12 (d, J=11.0 Hz, 1H), 3.88-4.01 (m, 4H), 2.97 (dt, J=13.2 and 2.9 Hz, 1H), 2.53 (dt, J=13.1 and 2.9 Hz, 1H), 2.33 (ft, J=13.2 and 2.9 Hz, 1H), 1.62-1.81 (m, 3H), 1.23-1.35 (m, 1H).

1. filtrationThe catalyst was filtered
2. concentrationthe filtrate was concentrated
3. dissolutionThe residue was dissolved in 200 ml DCM
4. stirringThe mixture was stirred at room temperature for ten minutes
5. washThe organic layer was washed with 1N HCl (100 ml), water (100 ml), brine (100 ml)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. dissolutionThe residue was dissolved in 200 ml THF
9. additionKOt-Bu (1M in THF, 14 ml) was added
10. stirringThe mixture was stirred at room temperature for twenty minutes
11. addition200 ml water and 200 ml EtOAc were added
12. washThe organic layer washed with brine (200 ml)
13. dry with materialdried over Na2SO4
14. concentrationconcentrated
15. customThe product was purified by column (EtOAc/hexane from 0/100 to 25/75 in 45 minutes)

ORD-Eintrag

ord-79e32558fba846f8a7501a4c55ebb14d

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08067621B2