Cesium carbonate → cis-N-{4-[(6-bromopyridin-3-yl)oxy]tetrahydrofuran-3-yl}propane-2-sulfonamide

HRID 2060811Notes

Reaction equation

HRID 2060811 reaction equation
CS(O[C@H:6]1[C@H:10]([O:11][C:12]2[CH:13]=[N:14][C:15]([Br:18])=[CH:16][CH:17]=2)[CH2:9][O:8][CH2:7]1)(=O)=O.[CH3:19][CH:20]([S:22]([NH2:25])(=[O:24])=[O:23])[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)(O)[O-].[Na+]>C(#N)C>[Br:18][C:15]1[N:14]=[CH:13][C:12]([O:11][C@H:10]2[CH2:9][O:8][CH2:7][C@H:6]2[NH:25][S:22]([CH:20]([CH3:21])[CH3:19])(=[O:24])=[O:23])=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 3549191Propane-2-sulfonamideHCID 86653036trans-4-[(6-Bromopyridin-3-yl)oxy]tetrahydrofuran-3-yl methanesulfonate

Product 1

HCID 86653038cis-N-{4-[(6-bromopyridin-3-yl)oxy]tetrahydrofuran-3-yl}propane-2-sulfonamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Trans-4-[(6-bromopyridin-3-yl)oxy]tetrahydrofuran-3-yl methane sulfonate (591.7 mg, 1.75 mmol), propane-2-sulfonamide (647 mg, 5.25 mmol) and cesium carbonate (855 mg, 2.62 mmol) were combined in acetonitrile (8 mL) and subjected to microwave irradiation for 55 minutes at 150° C. The crude reaction mixture was combined with several similar reactions run under the same conditions (total starting material used: 1.527 g, 4.515 mmol) and shaken with saturated aqueous sodium bicarbonate solution (100 mL). The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel chromatography (Gradient: 5% to 40% ethyl acetate in heptane) to provide the title compound. Yield: 382 mg, 1.046 mmol, 23%. 1H NMR (400 MHz, CDCl3) δ 1.34 (d, J=6.8 Hz, 3H), 1.36 (d, J=6.8 Hz, 3H), 3.17 (septet, J=6.8 Hz, 1H), 3.74 (dd, J=9, 9 Hz, 1H), 3.94 (dd, J=10.9, 1.5 Hz, 1H), 4.14 (dd, J=8, 8 Hz, 1H), 4.19 (dd, J=10.9, 4.3 Hz, 1H), 4.27 (m, 1H), 4.84 (m, 1H), 5.66 (d, J=9.9 Hz, 1H), 7.20 (dd, J=8.8, 3.2 Hz, 1H), 7.40 (d, J=8.8 Hz, 1H), 8.01 (d, J=3.2 Hz, 1H).

Workup

  1. customirradiation for 55 minutes at 150° C
  2. customThe crude reaction mixture
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via silica gel chromatography (Gradient: 5% to 40% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-6775c4b1cab247e09d44fe07c26a0047
Source dataset
uspto-grants-2012_10
Patent number
US08278457B2

Reaction notes

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