Trifluoroacetic acid → N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-([2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}-D-serine

Participants

Reaction Steps

A solution of [4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid (0.050 g, 0.103 mmol), O-(tert-butyl)-D-Serine tert-butyl ester hydrochloride (0.032 g, 0.147 mmol) and N-Methylmorpholine (0.035 ml, 0.318 mmol) in DCM (4 ml) was stirred at RT for 5 min, after which TBTU (0.044 g, 0.137 mmol) was added. After 3 h, the conversion to the ester (m/z: 683.1) was completed and the solution was added TFA (2 ml). After 22 h, the solvent was removed under reduced pressure and the residue (m/z: 571.1) was dissolved in MeOH (4 ml). To the solution were successively added small portions of NaBH4 (totally 0.130 g, 3.44 mmol) until the reduction was completed. The reaction mixture was added a 0.1M ammonium acetate buffer (3 ml) and the methanol was removed under reduced pressure. The remaining solution was purified by preparative HPLC using a gradient of 20-60% MeCN in 0.1M ammonium acetate buffer as eluent. After freeze-drying, 0.021 g (36% yield) of the desired product (as a mixture of diastereomers) was obtained as a white solid. M/z: 573.1. 1H NMR (DMSO, 400 MHz): δ 2.84-2.96 (m, 2H), 3.47 (dd, 1H), 3.69 (dd, 1H), 3.97-4.06 (m, 1H), 4.27-4.32 (m, 1H), 4.52 (ABq, 2H), 4.68-4.77 (m, 1H), 5.04-5.09 (m, 1H), 5.65 (bs, 1H), 6.99 (d, 2H), 7.07-7.41 (m, 10H), 7.89 (d, 1H).

Provenance & Evidence