Dimethylformamide → Z-Ala-Ala-Asn(Trt)-N(OCH3)CH3

Participants

Reaction Steps

The Weinreb amide Z-Ala-Ala-Asn(Trt)-N(OCH3)CH3 (3) was prepared according to the method of Yasuma, 1998: To a stirred solution of Z-Ala-Ala-Asn(Trt)-OH (0.5 g, 0.77 mmol), N,O-dimethylhydroxylamine hydrochloride (79 mg, 0.81 mmol), and triethylamine (114 μl, 0.82 mmol) in dry DMF (3 ml) were added diisopropylcarbodiimide (131 μl, 0.85 mmol) and HOBt (115 mg, 0.85 mmol) at 0° C., and the whole was stirred for 16 h during which time it was allowed to warm to room temperature. The mixture was concentrated under reduced pressure. The obtained crude compound was dissolved in CH2Cl2 (25 ml) and washed with aqueous citric acid, water, aqueous NaHCO3, brine (5 ml per washing step). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give the Weinreb amide as a white solid (0.49 g, 92%). The Weinreb amide was used without further purification.—TLC (MeOH/CHCl3, 1:30): Rf=0.49.—1H NMR (400 MHz, CDCl3): δ=1.26 (d, 3 H, J=7.0 Hz, CH3), 1.29 (d, 3 H, J=7.0 Hz, CH3), 2.64-2.76 (m, 2 H, CHCH2), 2.86 (s, 3 H, NCH3), 3.66 (s, 3 H, OCH3), 3.76-3.83 (m, 1 H, CH), 4.07-4.13 (m, 1 H, CH), 4.33-4.40 (m, 1 H, CH), 5.02-5.09 (m, 2 H, CH2O), 7.13-7.34 (m, 20 H, aryl-H).—MS (EI) m/z (%): 694 [M+H+], 716 [M+Na+], 732 [M+K+].

Provenance & Evidence