Reaktion #9629

Reaktionsgleichung

tert-Butyl bromoacetate

n-Butyllithium

Diisopropylamine

Methyl tetrahydro-2H-pyran-4-carboxylate

→

methyl 4-(2-tert-butoxy-2-oxoethyl)tetrahydro-2H-pyran-4-carboxylate

Ausbeute 56.8%

Lösungsmittel

Water

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   workup.ADDITIONwas added neat at −35° C
3. 3
   Temperaturto warm to 0° C.
4. 4
   workup.STIRRINGstirred for 2 h
5. 5
   workup.STIRRINGThe mixture was stirred at rt overnight
6. 6
   Extraktionthe mixture extracted with ethyl acetate
7. 7
   WaschenThe organic phase was washed with brine
8. 8
   Trocknendried over sodium sulfate
9. 9
   SonstigeThe crude product was purified by flash chromatography (Biotage Flash 40M, 6:1 hexane/ethyl acetate)

Vorschrift

Diisopropylamine (1.28 mL, 9.16 mmol) was diluted with tetrahydrofuran (2 mL) and cooled to −78° C. n-Butyllithium (2.5 M, 3.66 mL, 9.16 mmol) was added dropwise, and the solution was allowed to stir for 1 h. Methyl tetrahydro-2H-pyran-4-carboxylate (1.1 g, 7.63 mmol) was added as a solution in tetrahydrofuran (1.5 mL) at −78° C. The mixture was allowed to warm to −35° C. and stirred for 1 h. tert-Butyl bromoacetate (1.58 mL, 10.7 mmol) was added neat at −35° C. The mixture was allowed to warm to 0° C. and stirred for 2 h. The mixture was stirred at rt overnight. Water was added at 0° C. and the mixture extracted with ethyl acetate. The organic phase was washed with brine, and dried over sodium sulfate. The crude product was purified by flash chromatography (Biotage Flash 40M, 6:1 hexane/ethyl acetate) to afford methyl 4-(2-tert-butoxy-2-oxoethyl)tetrahydro-2H-pyran-4-carboxylate (1.12 g, 56%). LC-MS ret. time 2.47 min, m/z 258.7 (MH+); 1H NMR (300 MHz, CDCl3) δ 1.38 (s, 9H), 1.52–1.61 (m, 2H), 2.00–2.07 (m, 2H), 2.50 (s, 2H), 3.52–3.60 (m, 2H), 3.70 (s, 3H), 3.71–3.77 (m, 2H).

Quelle