Phenylboronic Acid → N-[(3S,4S)-4-(biphenyl-4-yloxy)tetrahydrofuran-3-yl]propane-2-sulfonamide

HRID 2360326Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2360326
Br[C:2]1[CH:20]=[CH:19][C:5]([O:6][C@@H:7]2[CH2:11][O:10][CH2:9][C@@H:8]2[NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])=[CH:4][CH:3]=1.[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[F-].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:2]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:20]=[CH:19][C:5]([O:6][C@@H:7]2[CH2:11][O:10][CH2:9][C@@H:8]2[NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 66827Phenylboronic AcidHCID 522689Potassium FluorideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67194268N-((3S,4S)-4-(4-Bromophenoxy)tetrahydrofuran-3-yl)propane-2-sulfonamide

Produkt 1

HCID 58248017N-[(3S,4S)-4-(biphenyl-4-yloxy)tetrahydrofuran-3-yl]propane-2-sulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 167845palladium(II) acetateKatalysator

Versuchsvorschrift

To a microwave vial was added N-[(3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-yl]propane-2-sulfonamide (124 mg, 0.340 mmol), phenylboronic acid (63.5 mg, 0.521 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (XPhos, 16.2 mg, 0.034 mmol), palladium(II) acetate (5.2 mg, 0.023 mmol) and potassium fluoride (99.6 mg, 1.71 mmol). The vial was capped, and purged three times with nitrogen/vacuum. A 1:1 mixture of degassed methanol/toluene (1.5 mL) was added and the reaction was subjected to microwave irradiation at 130° C. for 30 minutes. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate and saturated aqueous sodium chloride solution. The aqueous layer was extracted twice with ethyl acetate, and the organic layers were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (Gradient: 10% to 25% ethyl acetate in heptane), to afford the title compound as a solid. Yield: 90 mg, 0.25 mmol, 73%. 1H NMR (400 MHz, CDCl3) δ 1.37 (d, J=6.8 Hz, 3H), 1.40 (d, J=6.8 Hz, 3H), 3.17 (septet, J=6.8 Hz, 1H), 3.76 (dd, J=8.6, 8.6 Hz, 1H), 4.01 (dd, J=10.6, 1.6 Hz, 1H), 4.16-4.30 (m, 3H), 4.84 (m, 1H), 5.09 (d, J=9.4 Hz, 1H), 6.97 (d, J=8.7 Hz, 2H), 7.34 (t, J=7.4 Hz, 1H), 7.44 (dd, J=7.6, 7.6 Hz, 2H), 7.55 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 16.48, 16.55, 54.27, 55.35, 70.29, 71.96, 75.87, 115.85, 126.65, 126.88, 128.34, 128.68, 135.11, 140.25, 155.93.

Aufarbeitung

  1. customThe vial was capped
  2. custompurged three times with nitrogen/vacuum
  3. additionA 1:1 mixture of degassed methanol/toluene (1.5 mL)
  4. additionwas added
  5. customirradiation at 130° C. for 30 minutes
  6. customThe solvent was removed in vacuo
  7. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium chloride solution
  8. extractionThe aqueous layer was extracted twice with ethyl acetate
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by silica gel chromatography (Gradient: 10% to 25% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-a134858d35e7441a9530c81d4b72b003
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08686043B2

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