反应详情

温度

0 °C

4-(5-Isopropoxy-2-methyl-4-nitro-phenyl)-1-methyl-pyridinium iodide from the previous step (0.697 mmol) is dissolved in CH3OH (20 mL) and cooled to 0° C. NaBH4 (264 mg, 6.97 mmol, 10 equiv.) is slowly added. After this addition is complete, the cooling bath is removed and the reaction is stirred at room temperature for 1 h. The reaction is quenched by the slow addition of 1N aqueous HCl (14 mL). The CH3OH is partially removed by vacuum. The resulting residue is partitioned between EtOAc and 1 N aqueous NaOH. Additional 50% aqueous NaOH is added until the aqueous layer pH >12. The EtOAc layer is washed with 1 N aqueous NaOH (2×), the organic layer is then dried over Na2SO4, filtered, and concentrated under vacuum. After concentration, the crude product (175 mg) is dissolved in acetic acid (10 mL). TFA (0.15 mL, 3 equiv.) and PtO2 (53 mg, 30% w/w) are added and the reaction is placed under 50 psi H2 gas in a Parr Shaker for 14 h. The reaction mixture is filtered and the filtrate is concentrated under vacuum. The resulting residue is partitioned between EtOAc and 1 N aqueous NaOH. Additional 50% aqueous NaOH is added until the aqueous layer pH >12. The EtOAc layer is washed with 1 N aqueous NaOH (2×), the organic layer is then dried over Na2SO4, filtered, and concentrated under vacuum to give 2-Isopropoxy-5-methyl-4-(1-methyl-piperidin-4-yl)-phenylamine which is used in Step 4 without further purification: ESMS m/z 263.2 (M+H+).

1. additionAfter this addition
2. customthe cooling bath is removed
3. customThe reaction is quenched by the slow addition of 1N aqueous HCl (14 mL)
4. customThe CH3OH is partially removed by vacuum
5. customThe resulting residue is partitioned between EtOAc and 1 N aqueous NaOH
6. additionAdditional 50% aqueous NaOH is added until the aqueous layer pH >12
7. washThe EtOAc layer is washed with 1 N aqueous NaOH (2×)
8. dry with materialthe organic layer is then dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under vacuum
11. concentrationAfter concentration
12. dissolutionthe crude product (175 mg) is dissolved in acetic acid (10 mL)
13. waitthe reaction is placed under 50 psi H2 gas in a Parr Shaker for 14 h
14. filtrationThe reaction mixture is filtered
15. concentrationthe filtrate is concentrated under vacuum
16. customThe resulting residue is partitioned between EtOAc and 1 N aqueous NaOH
17. additionAdditional 50% aqueous NaOH is added until the aqueous layer pH >12
18. washThe EtOAc layer is washed with 1 N aqueous NaOH (2×)
19. dry with materialthe organic layer is then dried over Na2SO4
20. filtrationfiltered
21. concentrationconcentrated under vacuum