Methyl iodide → (2S,4S)-1-tert-butyl 2-methyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate

Temperatur

0 °C

To a solution of (2S,4S)-1-tert-butyl 2-methyl 4-(hydroxymethyl)pyrrolidine-1,2-dicarboxylate (2.57 g, 9.9 mmol) in CH2Cl2 (50 mL) was added AgOTf (4.07 g, 15.8 mmol) and 2,6-di-tert-butylpyridine (4.4 mL, 19.8 mmol). The reaction mixture was cooled to 0° C. (external temperature, ice bath) and MeI (0.98 mL, 15.8 mmol) was slowly added. The resulting slurry was stirred at 0° C. for 1.5 h and at room temperature for 1.5 h. The slurry was diluted with CH2Cl2 and filtered through celite. The filtrate was concentrated to dryness, dissolved in Et2O, and washed with HCl (1N) and brine. The aqueous layers were backextracted with Et2O and the combined organic layers were dried over Na2SO4 and concentrated. The crude oil was purified by silica gel chromatography (10% to 75% to 100% EtOAc/Hexanes) to provide (2S,4S)-1-tert-butyl 2-methyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate (2.11 g, 78%). 1H-NMR: 400 MHz, (CDCl3) δ: (mixture of rotamers, major reported) 4.20 (t, 1H), 3.71 (s, 3H), 3.67 (m, 1H), 3.34 (m, 2H), 3.30 (s, 3H), 3.16 (t, 1H), 2.43 (m, 2H), 1.74 (m, 1H), 1.38 (s, 9H).

1. additionwas slowly added
2. filtrationfiltered through celite
3. concentrationThe filtrate was concentrated to dryness
4. dissolutiondissolved in Et2O
5. washwashed with HCl (1N) and brine
6. dry with materialthe combined organic layers were dried over Na2SO4
7. concentrationconcentrated
8. customThe crude oil was purified by silica gel chromatography (10% to 75% to 100% EtOAc/Hexanes)

ORD-Eintrag

ord-bbe635c7c7474ec49f34b7192a864576

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09221833B2