Sodium Carbonate → HCID 59178383, Verbindung

Temperatur

17.5 °C

Crude 1-cyclopropyl-2-methoxyethanamine from the previous step was dissolved in CH2Cl2/H2O (300 mL/300 mL) and Na2CO3 (111.9 g, 1.06 mol) was added. The reaction mixture was placed in an ice bath and CbzCl (16.46 g, 96.78 mmol) was added via syringe. During the addition, the internal reaction mixture temperature was maintained at 15-20° C. After the addition was complete, the reaction mixture was stirred at room temperature for 2 h. The mixture was poured into a separatory funnel, diluted with H2O, (300 mL), and extracted with CH2Cl2 (3×300 mL). The combined organic layers were washed with brine (300 mL), dried over MgSO4, filtered and concentrated. The product was purified by column chromatography on silica gel (30% ethyl acetate in hexanes) to furnish benzyl 1-cyclopropyl-2-methoxyethylcarbamate (17.2 g, 78% yield for 2 steps) as an oil which crystallized upon standing: mp 190.5-192° C.; 1H NMR (400 MHz, DMSO-d6) δ 7.39-7.29 (m, 5H), 7.17 (d, J=8.5 Hz, 1H), 5.00 (s, 2H), 3.36-3.34 (m, 2H), 3.23 (s, 3H), 3.19-3.14 (m, 1H), 0.85-0.79 (m, 1H), 0.43-0.37 (m, 1H), 0.35-0.22 (m, 2H), 0.20-0.16 (m, 1H); LRMS (ESI) mile 250.3 [(M+H)+, calcd for C14H20NO3 250.1].

1. customThe reaction mixture was placed in an ice bath
2. additionDuring the addition
3. additionAfter the addition
4. additionThe mixture was poured into a separatory funnel
5. extractionextracted with CH2Cl2 (3×300 mL)
6. washThe combined organic layers were washed with brine (300 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe product was purified by column chromatography on silica gel (30% ethyl acetate in hexanes)

ORD-Eintrag

ord-14826a4b6ea84dd188794572df1bb0b6

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08372847B2