2-Aminooxazole → 5(S)-Oxazol-2-ylaminomethyl-3-(3-fluoro-4-(3,6-dihydro-(2H)-pyran-4-yl)phenyl)oxazolidin-2-one

To a stirred partial solution of 2-aminooxazole(169 mg, 2.0 mmol) in dry THF (10 ml), cooled to −78° C., under argon, was added slowly n-BuLi(1.33M, 1.5 ml, 2.0 mmol), followed after 1 h by 5(R)-methylsulfonyloxymethyl-3-(3-fluoro-4-(3,6-dihydro-(2H)-pyran-4-yl)phenyl)oxazolidin-2-one (see Example 41; 371 mg, 1.0 mol) suspended in dry THF(20 ml). The reaction was allowed to come to room temperature and then refluxed for 24 h. The reaction was quenched with ammonium chloride solution(10%w/v, 30 ml), extracting the mixture with chloroform (3×50 ml). The extracts were dried (magnesium sulfate), concentrated by rotary evaporation chromatographed by MPLC (Merck 9385 silica, 3-10% gradient methanol/dichloromethane eluent) and the pure fractions combined, concentrated and triturated with diethyl ether to. give the title compound (25 mg, 4.6%). NMR (300 Mz, DMSO-d6), δ/ppm: 2.31 (m, 2H), 3.35 (m, 2H, obscured), 3.64 (dd, 1H), 3.84 (t, 2H), 3.90 (m, 1H), 4.15 (m, 1H), 4.24 (m, 2H), 4.46 (m, 1H), 5.97 (m, 1H), 6.90 (m, 1H), 7.19 (m, 2H, partially obscured), 7.37 (dd, 1H), 7.44 (dd, 1H). MS: ES+ (M+H)=360.

1. customto come to room temperature
2. temperaturerefluxed for 24 h
3. customThe reaction was quenched with ammonium chloride solution(10%w/v, 30 ml),
4. extractionextracting the mixture with chloroform (3×50 ml)
5. dry with materialThe extracts were dried (magnesium sulfate)
6. concentrationconcentrated by rotary evaporation
7. customchromatographed by MPLC (Merck 9385 silica, 3-10% gradient methanol/dichloromethane eluent)
8. concentrationconcentrated
9. customtriturated with diethyl ether to

ORD record

ord-9c4c17896ab8406392af38a7a5bd9ace

Source dataset

uspto-grants-2004_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06734200B1