Water → Ethyl 1,8-dioxa-2-azaspiro[4.5]dec-2-ene-3-carboxylate

To a well-vented 500 mL three-necked round-bottom flask was added methyl triphenylphosphonium bromide/sodium amide mixture (“instant ylide”, 22.9 g, 5.49 mmol) and dry ether (100 mL). The mixture was stirred at rt for 1 h and filtered through a glass-fritted funnel directly into a solution of tetrahydro-pyran-4-one (5.00 g, 4.99 mmol) in ether (20 mL). This mixture was stirred at rt for 4 h. Ethyl-2-chloro-2-(hydroxyamino)acetate (8.32 g, 5.49 mmol) in DCM (100 mL) was added dropwise via addition funnel over 3 h, and the mixture was stirred for 2.5 days. Water (100 mL) was added, and the mixture was extracted three times with DCM (200 mL, 100 mL, 100 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 200-g Sepra Si 50 SPE column (Isco system: Flow rate=30 mL/min; Eluent=EtOAc/heptane, 1:9 v/v for 10 min, then 1:9 to 2:3 v/v over 40 min) to afford the title compound (3.00 g, 28%) as a tan oil. 1H-NMR (400 MHz, CDCl3) δ: 4.35 (q, J=7.2 Hz, 2H), 3.89 (ddd, J=11.8, 8.7, 3.3 Hz, 2H), 3.65-3.75 (m, 2H), 2.99 (s, 2H), 1.89-1.97 (m, 2H), 1.76-1.86 (m, 2H), 1.37 (t, J=7.2 Hz, 3H).

1. stirringThis mixture was stirred at rt for 4 h
2. stirringthe mixture was stirred for 2.5 days
3. extractionthe mixture was extracted three times with DCM (200 mL, 100 mL, 100 mL)
4. dry with materialThe combined organic extracts were dried over MgSO4
5. concentrationconcentrated in vacuo
6. customThe residue was purified on a 200-g Sepra Si 50 SPE column (Isco system
7. waitEluent=EtOAc/heptane, 1:9 v/v for 10 min

ORD-Eintrag

ord-1b9b090f234f42eb8fd59b3850fae339

Quelldatensatz

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08232409B2