Sodium hydride → Tert-butyl 4-(2-methoxy-2-oxoethylidene)piperidine-1-carboxylate

Temperatur

0 °C

60% sodium hydride in mineral oil (7.92 g, 198.02 mmoles) was washed with hexanes then suspended in N,N-dimethylformamide (220.00 mL). The mixture was cooled to 0° C. Trimethyl phosphonoacetate (29.0 mL, 189.82 mmoles) was added drop-wise to the reaction. The mixture was held at 0° C. with stirring on and held for 20 min. A solution of N-tert-butoxycarbonyl-4-piperidone (30.41 g, 152.62 mmoles) in 80 mL N,N-dimethylformamide was added to the mixture drop-wise. Reaction was stirred at room temperature for 3 hours. Mixture was diluted with diethyl ether (650 mL). Mixture was washed once with water. Aqueous layer was back extracted once with diethyl ether. Organic layers were combined. The mixture was washed 4 times with water and the aqueous phase was discarded. The mixture was washed with brine and the aqueous phase was discarded. The material was dried over MgSO4, filtered, and concentrated to dryness. Title compound was obtained as white solid in 92% yield. 1H NMR (300 MHz, CDCl3): δ=5.68 (s, 1H), 3.66 (s, 3H), 3.40-3.51 (m, 4H), 2.90 (t, J=5.49, 2H), 2.25 (t, J=5.49, 2H), 1.44 (s, 9H).

1. customto the reaction
2. customwas held at 0° C.
3. customReaction
4. stirringwas stirred at room temperature for 3 hours
5. washMixture was washed once with water
6. extractionAqueous layer was back extracted once with diethyl ether
7. washThe mixture was washed 4 times with water
8. washThe mixture was washed with brine
9. dry with materialThe material was dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated to dryness

ORD-Eintrag

ord-eb976de765da4f0da116f00a32f3414e

Quelldatensatz

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07384931B2