Reaction Steps
To a solution of 2-chloro-N-methoxy-N-methylacetamide (6.0 g, 48.8 mmol) in dry DMF (20 mL) at 23° C. was added 3-mercaptophenol (4.44 mL, 48.8 mmol) and K2CO3 (6.7 g, 48.8 mmol). The resulting suspension was stirred at 23° C. overnight. After this period of time, Merrifield resin (24 g, <2 mmol·g−1, <48.8 mmol) was added to the mixture followed by K2CO3 (11.4 g, 83.0 mmol) as well as TBAI (catalytic amount), and the suspension was heated up to 50° C. After 12 hours at this temperature, the resin was filtered and washed several times: HClaq. (50 mL), MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL). The resin was dried under reduced pressure to constant mass of 29.2 g. The final mass gain (5.2 g, 27.3 mmol) indicated an estimate loading of 0.81 mmol·g−1. Resin 2-49 (10 g, 0.81 mmol·g−1) was suspended in a 1:1 mixture of HFIP/CH7Cl2 (50 mL). To this suspension, H2O2 (3 mL, 16.0 mmol) was added at 23° C. and the resulting mixture was shaken for 12 h. Resin 2-113 was then filtered, washed using MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL) and dried under reduced pressure to constant mass before subsequent use. Resin 2-113 (4.0 g, <0.81 mmol·g−1) was suspended in DMSO (40 mL) followed by the addition of tBuOK (336 mg, 3.0 mmol). After shaking the reaction for 1 h at room temperature, 5-iodo-1-pentene (588 mg, 3.0 mmol) was added to the suspension and the mixture was shaken for 3 h. The resin was filtered, washed and dried as before. Then, it was suspended in toluene and heated at 80° C. After 8 h at this temperature, the resin was filtered and washed several times with more toluene. The combined toluene solutions were evaporated giving pure compound 2-114 as a colourless oil (321 mg, 77%) of 95% purity judged by NMR. 1H NMR (400 MHz, CDCl3, 25° C.): δ=6.94 (dt, J=15.7, 6.7 Hz, 1H), 6.39 (d, J=15.2 Hz, 1H), 5.84-5.74 (m, 1H), 5.02 (dd, J=17.4, 1.7 Hz, 1H), 4.97 (d, J=10.1 Hz, 1H), 3.67 (s, 3H), 3.21 (s, 3H), 2.34-2.29 (m, 2H), 2.23-2.18 (m, 2H); 13C NMR (100 MHz, CDCl3, 25° C.): δ=166.8, 146.7, 137.3, 119.1, 115.3, 61.6, 32.3, 31.7, (one carbon is not detected); I.R. (film): νmax=2934, 1681, 1638, 1378, 1179 cm−1.
