反应详情

To a suspension of NaH (2.7 mg, 68 μmol, 60% oil dispersion) in DMF (0.1 mL) was added a solution of {[4-(2′-hydroxymethyl-6′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (30 mg, 56.4 μmol) in DMF (0.1 mL), as prepared according to the procedure of step b of Example 213. The mixture was stirred at ambient temperature for 30 min, and then placed in an ice-water bath. After 20 min, a solution of ethyl 3-bromopropionate (8.6 μL, 67.0 μmol) in DMF (0.05 mL) was added once. Ice-water bath was removed, and the mixture was stirred for 16 h. H2O was added, and the mixture was extracted with EtOAc (3×). The extracts were combined, washed with H2O, dried over Na2SO4, concentrated, and flash chromatographed on silica gel, eluting with EtOAc/DCM (15%) followed by EtOAc/hexane (40%) to give the title compound (9 mg, 25%) yield) as an oil.

1. customas prepared
2. customplaced in an ice-water bath
3. waitAfter 20 min
4. customIce-water bath was removed
5. stirringthe mixture was stirred for 16 h
6. additionH2O was added
7. extractionthe mixture was extracted with EtOAc (3×)
8. washwashed with H2O
9. dry with materialdried over Na2SO4
10. concentrationconcentrated
11. customflash chromatographed on silica gel
12. washeluting with EtOAc/DCM (15%)