Phenylacetyl chloride → (3R,5S)-5-Phenylacetylamino-piperidine-3-carboxylic acid cyclopropyl-[4-(3-methoxy-propyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-amide

Participants

Reaction Steps

(3R,5S)-3-{Cyclopropyl-[4-(3-methoxy-propyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo-[1,4]oxazin-6-yl]-carbamoyl}-5-phenylacetylamino-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (90 mg, 0.12 mmol) is treated with 4N HCl/AcOEt (2 mL) at r.t. for 1 hr, then evaporated. The evaporated residue is dissolved in CH2Cl2 (1 mL). To the solution is added phenylacetyl chloride (20.4 mg, 0.132 mmol) and diisopropyl ethyl amine (32 mg, 0.264 mmol) at 0° C. and stirred for 40 min. After adding 1N HClaq, the mixture is extracted with CH2Cl2, washed with sat NaHCO3aq, brine and dried (MgSO4). Concentration under vacuum and the evaporated residue is dissolved in THF (1 mL). To the solution is added DBU (9 mg, 0.06 mmol) and N-(2-mercaptoethyl)aminoethyl polystyrene (2.1 mmol/g, 286 mg, 0.6 mmol) and stirred for 1 h at r.t. The reaction mixture is filtered via celite pad and washed with THF. Concentration under vacuum and purification with RP-HPLC gives the title compound. MS: 549 [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 2.78 min.

Provenance & Evidence