(2R)-2-hydroxy-3,3-dimethylbutanoic acid → HCID 58760151, compound

Participants

Reaction Steps

The title compound was prepared from N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide (hydrochloride salt, Example 26, Step B, 55 mg, 0.16mmol) and (2R)-hydroxy-3,3-dimethylbutyric acid (22 mg, 0.16 mmol) essentially according to the EDC coupling procedure described in Example 27, Step C (without the deprotection step). The mixture was stirred for 18 h at ambient temperature and was then concentrated in vacuo. The residue was purified directly by semi-preparative HPLC using a Waters Xterra RP8 column (1.9 cm×30 cm) using a 30 minute gradient of 95/5-water/MeCN to 100% MeCN with 0.1% TFA as the mobile phase at a flow rate of 20 mL/min. The product-containing fractions were concentrated in vacuo to afford the title compound as a white crystalline solid (62 mg). HPLC RT=2.86 min (Method A); LCMS m/z=421.3; 1H NMR (400 MHz, CDCl3): δ 9.15 (s, 1H), 7.62 (d, J=2.2 Hz, 1H), 7.51 (br m, 1H), 7.44 (dd, J=2.2, 8.4 Hz, 1H), 7.25 (d, J=8.6 Hz, 1H), 4.5 (dd, J=3.8, 8.6 Hz, 1H) 4.25 (d, J=5.3 Hz, 1H), 4.2 (m, 1H), 4.15 (s, 1H) 3.69 (m, 1H), 3.57 (m, 1H), 2.73 (br s, 1H), 1.8–2.1 (m, 4H), 1.0 (s, 9H)).

Provenance & Evidence