| 32% |
Stage #1: sodium prop-2-ene-1-sulfonate With bromine In water at 20℃; for 3h;
Stage #2: With hydrogenchloride In water at 20℃; for 24h; |
1
Preparation of (Z)-3-(tert-butylamino)prop-1-ene-1-sulfonic acid (Compound N20); To a boiling solution of allyl bromide (21.6 mL, 250 mmol) in a solvent mixture of EtOH and H2O (200 mL, v/v=3:1) was added dropwise a solution of sodium sulfite (15.75 g, 125 mmol) in water (60 mL). The reaction mixture was heated under reflux for 3 hours, and concentrated to dryness under reduced pressure. The obtained white solid was suspended in EtOH in water (130 mL, 90%), heated for 30 minutes, cooled to room temperature, and collected by filtration, giving sodium prop-2-ene-1-sulfonate (14 g, 76%); 1H NMR (500 MHz, D2O) δ 3.55 (d, J=7.3 Hz, 2H), 5.35-5.41 (m, 2H), 5.85-6.00 (m, 1H). To a stirred solution of sulfonate obtained from step 1 (12.0 g, 84 mmol) in water (48 mL) was added bromine (about 4.5 mL) dropwise with stirring until the solution turned pale brown. The solution was stirred at room temperature for 3 hours. A small amount of Na2SO3 was added to destroy the excess bromine. The solvent was then removed in vacuo and a white solid was obtained. Without further purification, the 2,3-dibromo-1-propanesulfonate was treated with concentrated HCl (50 mL) by stirring at room temperature for 1 day. The precipitate (inorganic salt) was removed by filtration. The filtrate was concentrated to yellow syrup. Without further purification, the syrup residue was subjected to vacuum distillation at 140-150° C. to give 2-bromo-1,3-propane sultone (6.5 g, 32%); 1H NMR (500 MHz, CDCl3) δ 3.52 (dd, J=14.0 & 7.0 Hz, 1H), 3.88 (dd, J=14.0 & 7.0 Hz, 1H), 4.50-4.60 (m, 1H), 4.70-4.82 (m, 2H). To a solution of 2-bromo-1,3-propane sultone (obtained in Step 2, 8.0 g, 39.80 mmol) in toluene (200 mL) was added NEt3 (9 mL, 65 mmol). The reaction mixture was stirred for 3 h (or until complete consumption of the starting material), diluted with an aqueous solution of HCl (1 M), and extracted twice with EtOAc. The organic layer was dried over Na2SO4 and concentrated to give 1,3-prop-1-ene sultone (4.5 g, 94%) as a white solid; 1H NMR (500 MHz, CDCl3) δ 5.11 (dd, J=2.2 & 2.2 Hz, 2H), 6.80 (dt, J=6.6 & 2.2 Hz, 1H), 7.00 (dt, J=6.6 & 2.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 72.54, 124.76, 137.04. To a solution of 1,3-prop-1-ene sultone (obtained in step 3, 36 mg, 3 mmol) in THF (5 mL) was added tert-butylamine (316 μL, 3 mmol). The reaction mixture was refluxed for 4 h, and then concentrated to dryness. The residual solid material was suspended in a solvent mixture of EtOH, acetone and ether, heated for 15 minutes, and cooled to room temperature. The solid was collected by filtration, washed with ether then dried, providing the title compound (130 mg, 22%); 1H NMR (500 MHz, D2O) δ 1.24 (s, 9H), 4.00 (d, J=7.0 Hz, 2H), 5.94 (m, 1H), 6.50 (d, J=11.0 Hz, 1H). 13C NMR (125 MHz, D2O) δ 25.08, 37.84, 57.63, 127.81, 136.08. ES-MS 192 (M-1). |
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