Water → HCID 18187953, compound

Temperature

-78 °C

A 1M solution of sodium hexamethyldisilazane (NaHMDS, 350 mL, 0.35 mol) in THF was added slowly to a suspension of (methoxymethyl)triphenyl phosphonium chloride (120 g, 0.35 mol,) in THF (100 mL) at −78° C. under N2. The resulting brown solution was stirred at −78° C. for 20 minutes and then 1-carbethoxy-4-piperidone (50 g, 0.292 mol) in THF (50 mL) was added dropwise. The mixture was stirred at −78° C. for 5 minutes and then for 2 hours at room temperature. Water (200 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts were dried over Na2SO4. The solvent was evaporated to give an orange solid which was suspended in Et2O (200 mL). The solid was removed by filtration and the filtrate was concentrated to give a yellow oil which was triturated with hexane (200 mL). The white solid which precipitated was removed by filtration. The filtrate was concentrated in vacuo and this was procedure repeated twice more to give the title compound (52 g, 89%) as a pale yellow oil. TLC Rf=0.72 (EtOAc:hexane, 1:2); 1H NMR (CDCl3) δ 5.84 (s, 1H), 4.11 (q, J=7 Hz, 2H), 3.54 (s, 3H), 3.37-3.42 (mult, 4H), 2.24 (t, J=5.6 Hz, 2H), 1.99 (t, J=5.6 Hz, 2H), 1.24 (t, J=7 Hz, 3H); 13C NMR (CDCl3) δ 1.55, 140.8, 113.4, 61.3, 59.5, 45.8, 44.6, 29.6, 25.2, 14.8; mass spectrum (API-TIS) m/z 200 (M+H). Anal Calcd for C10H17N1O3: C, 60.28; H, 8.60; 7.03. Found: C, 60.29; H, 8.63; N, 6.81.

1. stirringThe mixture was stirred at −78° C. for 5 minutes
2. waitfor 2 hours at room temperature
3. customthe layers were separated
4. extractionThe aqueous layer was extracted with EtOAc
5. dry with materialthe combined organic extracts were dried over Na2SO4
6. customThe solvent was evaporated
7. customto give an orange solid which
8. customThe solid was removed by filtration
9. concentrationthe filtrate was concentrated
10. customto give a yellow oil which
11. customwas triturated with hexane (200 mL)
12. customThe white solid which precipitated
13. customwas removed by filtration
14. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-96f464d790c2471bb184d3a19cc81cee

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06297260B1