反应详情

(2S)-di-tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypyrrolidine-1,2-dicarboxylate (A1) (1.58 g, 4.42 mmol, 1 eq.) was diluted in methanol (6 mL). To this mixture, hydrazine (0.417 mL, 13.26 mmol, 3 eq.) was added. The reaction was stirred at room temp. overnight then concentrated. To the residue, 0.5 N HCl (22.1 mL, 11.05 mmol, 2.5 eq.) was added and the mixture was sonnicated until the residue dissolved in the acid. The solution was cooled in an icewater bath. A 1.0 M solution of NaNO2 (5.3 mL, 5.3 mmol, 1.2 eq.) was added slowly and stirred for 15 min. A 1:1 benzene:chloroform mixture was added, the organic layer was separated and added slowly to refluxing benzene (2×). The reaction was refluxed for 1 hr then concentrated. Chromatography using DCM and 20% MeOH in DCM gave 0.978 g (2.86 mmol) of (8S)-di-tert-butyl 2-oxo-1-oxa-3,7-diazaspiro[4.4]nonane-7,8-dicarboxylate (B1) as a 4:1 (5S,8S:5S,8R) mixture of the diastereomers. 1H NMR (300 MHz, DMSO) 7.63 (m, 1H), 4.29-4.09 (m, 1H), 3.65-3.39 (m, 4H), 2.5-2.0 (m, 2H), 1.43-1.18 (m, 18H).

1. concentrationthen concentrated
2. dissolutiondissolved in the acid
3. temperatureThe solution was cooled in an icewater bath
4. stirringstirred for 15 min
5. customthe organic layer was separated
6. additionadded slowly
7. temperatureto refluxing benzene (2×)
8. temperatureThe reaction was refluxed for 1 hr
9. concentrationthen concentrated