反应详情

Cs2CO3 (38.0 g, 116.0 mmol) was added to a solution of Ex 3-Step 1 product (15.0 g, 58.0 mmol) in DMF (63 mL). Methyl iodide (3.74 mL, 58.2 mmol) was added and the resulting pink colored solution was stirred at rt for 2 hr. The mixture was concentrated and the residue was partitioned between EtOAc and water. The organic phase was separated and washed with brine, dried (MgSO4) and concentrated. Silica gel chromatography using 40% heptane/CH2Cl2 yielded 10.1 g (64%) of Ex 3-Step 2 product as a white solid. 1H NMR (CDCl3) showed ˜5% of the corresponding regioisomer (4-bromo-5-(4-chlorophenyl)-1-methyl-1H-pyrazole). The identities of the two regiosomers were established via NMR NOE (Nuclear Overhauser Effect) experiments. This material was used without further purification. 1H NMR (400 MHz, CDCl3) δ 7.80-7.82 (m, 2H), 7.43 (s, 1H), 7.35-7.38 (m, 2H), 3.90 (s, 3H).

1. concentrationThe mixture was concentrated
2. customthe residue was partitioned between EtOAc and water
3. customThe organic phase was separated
4. washwashed with brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. customyielded 10.1 g (64%) of Ex 3-Step 2 product as a white solid
8. customThis material was used without further purification