反应详情

温度

10 °C

Freebase formation was performed on a 200 gram scale. A 5 L, three necked, round-bottomed flask, equipped with an over head stirrer, thermometer, and addition funnel was charged with 200g (0.522 mol) of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine p-TSA salt and 1 L of water. The mixture was stirred and cooled to 10° C. The slurry was basified to a pH of about 11-12 by the slow addition of 200 ml of 6 N NaOH over a period of 15 min. The reaction mixture was diluted with 500 ml of brine (sodium chloride dissolved in water) and extracted with 3×1 L of dichloromethane. The combined organic phases were washed with 1.0 L of brine, dried over MgSO4, filtered and concentrated to dryness. The residue was triturated with 1 L of 1:1 IPAC:Heptane, the resulting slurry was stirred for 1 hour, filtered and the filter cake was washed with 2×250 ml of 1:1 mixture of IPAC:Heptane. The filter cake was collected and dried at 40° C. under high vacuum for 24 hours to give 94.1 grams (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine (85.5%) as a white solid. The chemical purity was 100% AUC as tested by HPLC, and the chiral purity was 100% AUC as tested by HPLC. 1H NMR and 13C NMR was used to confirm the structure: 1H NMR (300 MHz, DMSO-δ6) δ 6.6 (s, 2H), 2.8 (m, 2H), 2.5 (m, 2H, merged with DMSO peak), 2.2 (m, 1H), 1.9 (m, 1H), 1.5-1.3 (m, 4H), 0.85 (t, 3H); 13C NMR (300 MHz, DMSO-d6) δ 166.2, 144.8, 113.6, 54.2, 49.1, 30.0, 29.6, 25.2, 23.5, 12.3.

1. customA 5 L, three necked, round-bottomed flask, equipped with an over head stirrer
2. additionthermometer, and addition funnel
3. extractionextracted with 3×1 L of dichloromethane
4. washThe combined organic phases were washed with 1.0 L of brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. customThe residue was triturated with 1 L of 1:1 IPAC
9. stirringHeptane, the resulting slurry was stirred for 1 hour
10. filtrationfiltered
11. washthe filter cake was washed with 2×250 ml of 1:1 mixture of IPAC
12. customThe filter cake was collected
13. customdried at 40° C. under high vacuum for 24 hours