反应详情

To a solution of (Z)-N-hydroxybenzimidoyl chloride (770 mg, 4.95 mmol) and ethyl 2-bromohex-2-enoate (1.09 g, 4.95 mmol) in DCM (15 mL) was added triethylamine (2.07 mL, 14.85 mmol) over 5 minutes. After ˜50% of the addition was complete, a precipitate formed. Stirring was continued for 24 hr at rt. The reaction mixture was partitioned between Et2O (100 ml) and water (100 ml). The organic layer was washed with brine (100 ml), dried (MgSO4) and concentrated to afford a yellow oil. This oil was chromatographed on a 5×15 cm silica gel column, eluting with a 0-8% EtOAc/Hex gradient. The product containing fractions were concentrated to afford 343 mg of a waxy, white solid. This material was triturated with heptane. The solid contained no product. The mother liquor was concentrated to afford a partially purified semisolid residue. The portion of the residue that dissolved in ˜3 ml of hexane was chromatographed on a 12 gm Isco silica gel cartridge, eluting with a 0-1% EtOAc/Hex gradient. Fractions containing the product were concentrated to afford ethyl 3-phenyl-4-propylisoxazole-5-carboxylate (34 mg, 0.131 mmol, 2.65% yield) as a colorless oil. HPLC retention time=1.91 minutes (PHENOMENEX® Luna 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1% TFA over a 2 minute gradient. MS: (M+H)=260.23. 1H NMR (500 MHz, chloroform-d) δ ppm 0.90 (t, J=7.4 Hz, 3H), 1.45 (t, J=7.2 Hz, 3H), 1.53 (m, 2H), 2.80 (m, 2H), 4.46 (q, J=7.2 Hz, 2H), 7.45 (m, 1H), 7.50 (m, 2H), 7.59 (m, 2H).

1. additionAfter ˜50% of the addition
2. customa precipitate formed
3. customThe reaction mixture was partitioned between Et2O (100 ml) and water (100 ml)
4. washThe organic layer was washed with brine (100 ml)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. customto afford a yellow oil
8. customThis oil was chromatographed on a 5×15 cm silica gel column
9. washeluting with a 0-8% EtOAc/Hex gradient
10. additionThe product containing fractions
11. concentrationwere concentrated
12. customto afford 343 mg of a waxy, white solid
13. customThis material was triturated with heptane
14. concentrationThe mother liquor was concentrated
15. customto afford a partially purified semisolid residue
16. customwas chromatographed on a 12 gm Isco silica gel cartridge
17. washeluting with a 0-1% EtOAc/Hex gradient
18. additionFractions containing the product
19. concentrationwere concentrated