반응 #51451

ord-4680cbedb8364560ab87f775821d48ad

반응 조건

온도
80°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타was deoxygenated with a stream of argon for 15 minutes
  2. 2
    온도After cooling to room temperature
  3. 3
    기타the mixture was partitioned between ethyl acetate and pH 4 citrate buffer
  4. 4
    추출The aqueous layer was extracted twice with ethyl acetate
  5. 5
    세척the combined organic layers were washed with brine
  6. 6
    건조dried over sodium sulfate
  7. 7
    농축concentrated
  8. 8
    기타The residue was purified by chromatography on silica gel
  9. 9
    세척eluting with a gradient from dichloromethane to 5% methanol in dichloromethane

실험 절차

A mixture of 0.45 g (1.0 mmol) of 3(S)-4-(4-(4-bromophenoxy)benzenesulfonyl-tetrahydro-2H-1,4-thiazine-3-carboxylic acid and 0.11 g (1.0 mmol) of 3-furan boronic acid (J. Org. Chem. 1984, 49, 5237-5243) in 2 mL of benzene, 2 mL of 2M aq. sodium carbonate, and 1.5 mL of ethanol was deoxygenated with a stream of argon for 15 minutes, and then 115 mg (0.1 mmol) of tetrakis(triphenylphosphine)palladium was added and the mixture was heated at 80° C. for six days. After cooling to room temperature, the mixture was partitioned between ethyl acetate and pH 4 citrate buffer. The aqueous layer was extracted twice with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by chromatography on silica gel, eluting with a gradient from dichloromethane to 5% methanol in dichloromethane, to provide 3(S)-4-(4-(4-(furan-3-yl)phenoxy)benzenesulfonyl-tetrahydro-2H-1,4-thiazine-3-carboxylic acid (0.317 g, 67%) as a sticky solid foam. FAB+MS Calcd for M+Cs+=606.0021. Obs 606.0036; 1H NMR (CDCl3) δ 7.72-7.43 (m, 6H), 7.04 (d, 2H, J=8.46 Hz), 7.00 (d, 2H, J=8.82 Hz), 6.67 (s, 1H), 4.51 (s, 1H), 4.1-3.9 (bm, 1H), 3.7-3.6 (bm, 1H), 3.2-3.1 (bm, 1H), 2.42 (bd, 1H, J=12.87 Hz), 1.61 (s, 3H), 1.38 (s, 3H)

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US06849732B2uspto-grants-2005_02