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 back extracted 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 rotomers, 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. extractionThe aqueous layers were back extracted with Et2O
7. dry with materialthe combined organic layers were dried over Na2SO4
8. concentrationconcentrated
9. customThe crude oil was purified by silica gel chromatography (10% to 75% to 100% EtOAc/Hexanes)

ORD-Eintrag

ord-9ed3dc51d001401c8a6bdc9e6902aaf6

Quelldatensatz

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09156823B2