反应详情

A mixture of trans-2-chloro-N-(4-formyl-cyclohexyl)-5-trifluoromethyl-benzamide (Example 1 Step 3) (100 mg, 0.30 mmol) and 4-(4-chlorophenyl)isoxazol-3-amine (this compound can be prepared according to method described in ‘Chemistry of Heterocyclic Compounds’ (New York, N.Y., United States) (2007), 43(1), 118-119) (58 mg, 0.300 mmol) is stirred in titanium(IV) isopropoxide (1 ml, 3.4 mmol) for 3 h. A thick slurry results. After 3 h, methanol (5 ml) is added followed by slow addition of sodium borohydride (18 mg, 0.5 mmol). after 5 minutes, sodium hydroxide solution 91 ml, 0.1 M) is added to the reaction followed by dilution with ethyl acetate and brine. The organic extract is washed with brine, dried over MgSO4 and the solvent removed in vacuo. Purification by chromatography on silica, eluting with chloroform-ethanol (10:1) affords a sample of product containing minor amounts of starting materials. Trituation with methanol yields a pure sample or the title compound. MS m/z 512.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 1.25 8H, m), 1.75 (1H, m), 1.95 (2H, m), 2.22 (2H, m), 3.20 (2H, d), 4.00 (1H, m), 5.97 (1H, d), 7.35 (2H, d), 7.45 (2H, d), 7.55 (1H, d), 7.62 (1H, d), 7.90 (1H, s), 8.15 (1H, s).

1. customcan be prepared
2. customA thick slurry results
3. waitafter 5 minutes
4. extractionThe organic extract
5. washis washed with brine
6. dry with materialdried over MgSO4
7. customthe solvent removed in vacuo
8. customPurification by chromatography on silica
9. washeluting with chloroform-ethanol (10:1)
10. customaffords a sample of product
11. additioncontaining minor amounts of starting materials