反应详情

(R)-tert-butyl 4-((tert-butoxycarbonyl)amino)-3-oxopentanoate (702a; 34.3 g, 119 mmol) was treated with NH4OAc (Fluka; 92 g, 1194 mmol), NH3 (2 M in MeOH; Aldrich; 597 mL, 1194 mmol). To the resulting slurry was added chloroacetaldehyde (50% in water; Aldrich; 154 mL, 1194 mmol) in portions. The temperature of the reaction rose to 42° C. and the reaction was cooled with ice briefly, to 38° C. When no further exotherm was noted, the clear light yellow reaction was placed on a rotovap in a 50° C. water bath. After 40 min, the reaction was dark brown. The reaction was heated for an additional 100 min. The reaction was concentrated in vacuo and treated with DCM and sat'd aq. NaHCO3 with rapid stirring (CAUTION GAS EVOLUTION). The reaction was transferred to a 5 L bottle and solid NaHCO3 was added. When gas evolution was no longer observed and the material was transferred to a separatory funnel. (Noted a lot of chunky material that did not dissolve in DCM, used some MeOH to dissolve.) The water layer was extracted with 3×250 mL of DCM, and the combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulting thick brown oil was dissolved in ˜150 mL of DCM, filtered, and purified by silica gel chromatography (1500 g ISCO Redisep gold column) using 0-30% EtOAc/hexanes to elute product. The product-containing fractions were concentrated to afford (R)-tert-butyl 2-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrole-3-carboxylate (23.41 g, 75 mmol, 63% yield) as a white foam. 1H NMR (400 MHz, CDCl3) δ ppm 9.30 (1H, br. s.), 6.53 (2H, dt, J=13.9, 2.8 Hz), 6.10 (1H, br. s.), 5.15 (1H, br. s.), 1.57 (9H, s), 1.53 (3H, d, J=6.8 Hz), 1.43 (9H, s). m/z (ESI, +ve) 333.1 (M+Na)+.

1. customrose to 42° C.
2. temperaturethe reaction was cooled with ice briefly
3. customto 38° C
4. customthe clear light yellow reaction
5. customwas placed on a rotovap in a 50° C.
6. temperatureThe reaction was heated for an additional 100 min
7. concentrationThe reaction was concentrated in vacuo
8. additiontreated with DCM
9. additionwas added
10. customthe material was transferred to a separatory funnel
11. dissolution(Noted a lot of chunky material that did not dissolve in DCM
12. dissolutionto dissolve
13. extraction) The water layer was extracted with 3×250 mL of DCM
14. dry with materialthe combined organics were dried over anhydrous Na2SO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. dissolutionThe resulting thick brown oil was dissolved in ˜150 mL of DCM
18. filtrationfiltered
19. custompurified by silica gel chromatography (1500 g ISCO Redisep gold column)
20. washto elute product
21. concentrationThe product-containing fractions were concentrated