Chlorotrimethylsilane → HCID 131729734, compound

Participants

Reaction Steps

Methyl N-(tert-butoxycarbonyl)-2-nitro-5-phenoxy-L-phenylalaninate (91) Freshly distilled DMF (45 mL) was added to Zn powder (20.0 g, 306 mmol) under N2. Trimethylsilyl chloride (8.0 mL, ˜0.2 eq.) was added at RT and the resulting suspension was stirred vigorously for 35 min. The resulting pale orange supernatant was removed via syringe. The activated Zn was washed with DMF (2×30 mL). After removal of the DMF, the activated zinc was dried under vacuum using a heat gun. Methyl N-(tert-butoxycarbonyl)-3-iodo-L-alaninate (37.0 g, 112 mmol) was freshly recrystallized from petroleum ether, dried in vacuo, and dissolved in freshly distilled DMF (93 mL), and the solution was added to the activated zinc at 0° C. After 5 min, the cooling bath was removed. The reaction mixture was stirred for 20 min in a RT water bath, at which time TLC analysis indicated disappearance of the starting iodide. The grayish supernatant was transferred via syringe into a dry flask under N2, and the remaining zinc metal was washed with DMF (20 mL). To the flask containing the combined DMF fractions was added sequentially a solution of 2-bromo-1-nitro-4-phenoxybenzene (90) (30.0 g, 102 mmol) in DMF (18 mL), Pd(OAc)2 (1.1 g, 5.1 mmol), then dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (4.9 g, 10.2 mmol). The resulting brown solution was stirred at RT, and the solution turned red within 1 h. The reaction mixture was maintained at RT for 16 h. The reaction mixture was poured into EtOAc (400 mL), and the resulting suspension was filtered through Celite. The filtrate was washed with water (2×400 mL) and saturated aqueous sodium chloride solution (400 mL), and the separated aqueous phase was washed with EtOAc (2×150 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by silica gel chromatography (Gradient: 0% to 25% EtOAc in heptane) to provide the title compound as a pale yellow solid (27.9 g, 66%). LCMS m/z 415.1 (M−1). 1H NMR (500 MHz, CDCl3) δ 1.38 (s, 9H), 3.21 (dd, J=13, 9 Hz, 1H), 3.57 (dd, J=13.3, 5.2 Hz, 1H), 3.73 (s, 3H), 4.65-4.72 (m, 1H), 5.17 (br d, J=8 Hz, 1H), 6.87-6.92 (m, 2H), 7.07-7.10 (m, 2H), 7.24-7.27 (m, 1H), 7.44 (dd, J=7.9, 7.9 Hz, 2H), 8.03 (d, J=8.8 Hz, 1H).

Provenance & Evidence