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]

HRID 564323Notes

Reaction equation

HRID 564323 reaction equation
C(O[CH2:9][CH2:10][C:11]1([CH2:16][CH:17]2[CH:26]([S:27]([C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)(=[O:29])=[O:28])[C:25]3[C:20](=[C:21]([F:38])[CH:22]=[CH:23][C:24]=3[F:37])[O:19][CH2:18]2)[O:15][CH2:14][CH2:13][O:12]1)C1C=CC=CC=1.[H][H].CS(Cl)(=O)=O.CCN(CC)CC>C(OCC)(=O)C.[OH-].[OH-].[Pd+2].C(Cl)Cl.O>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([S:27]([C@@:26]23[CH2:9][CH2:10][C:11]4([O:15][CH2:14][CH2:13][O:12]4)[CH2:16][C@H:17]2[CH2:18][O:19][C:20]2[C:21]([F:38])=[CH:22][CH:23]=[C:24]([F:37])[C:25]3=2)(=[O:29])=[O:28])=[CH:31][CH:32]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 670057693-[2-(2-Benzyloxy-ethyl)-[1,3]dioxolan-2-ylmethyl]-4-(4-chloro-benzenesulfonyl)-5,8-difluoro-chromanHCID 178418361HCID 178418361, compound

Product 1

HCID 86614614Trans-10a-[(4-chlorophenyl)sulfonyl]-1,4-difluoro-6a, 9,10,10a-tetrahydrospiro[6H-dibenzo[b,d]pyran-8(7H), 2'-[1,3]dioxolane]

Reagents, catalysts & solvents 4

HCID 9942167Palladium hydroxideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-79e32558fba846f8a7501a4c55ebb14d
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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