Reaktion #1859309

Reaktionsgleichung

2-chloro-4-iodo-pyridine

tri(2-furyl)-phosphine

dibromomethane

chlorotrimethylsilane

1-(tert-butoxycarbonyl)-3-iodoazetidine

→

117a

Ausbeute 57.1%

tert-Butyl 3-(6-Chloropyridin-3-yl)azetidine-1-carboxylate

Ausbeute 57.1%

Lösungsmittel

DMF

DMF

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA 250-mL round-bottomed flask equipped with a magnetic stirrer
2. 2
   Temperaturreflux condenser
3. 3
   Temperaturthe reaction mixture was cooled to room temperature
4. 4
   workup.STIRRINGThe resulting mixture was stirred at room temperature for 30 min
5. 5
   workup.STIRRINGAfter stirring at 40° C. for 1 h
6. 6
   workup.STIRRINGAfter stirring at 70° C. for 16
7. 7
   Sonstigethe reaction mixture was partitioned between saturated aqueous ammonium chloride (200 mL) and diethyl ether (200 mL)
8. 8
   SonstigeThe layers were separated
9. 9
   Extraktionthe aqueous phase was extracted with diethyl ether (200 mL)
10. 10
    Trocknendried over sodium sulfate
11. 11
    Filtrationfiltered
12. 12
    EinengenThe filtrate was concentrated under reduced pressure
13. 13
    SonstigeThe resulting residue was purified by column chromatography

Vorschrift

A 250-mL round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with zinc (2.54 g, 38.9 mmol), DMF (32 mL), and dibromomethane (736 mg, 4.24 mmol). After stirring at 70° C. for 10 min, the reaction mixture was cooled to room temperature, and chlorotrimethylsilane (423 mg, 3.89 mmol) was added. The resulting mixture was stirred at room temperature for 30 min, and a solution of 1-(tert-butoxycarbonyl)-3-iodoazetidine (9.31 g, 38.9 mmol) in DMF (32 mL) was added. After stirring at 40° C. for 1 h, a solution of 2-chloro-4-iodo-pyridine (10.0 g, 35.3 mmol) in DMF (16 mL) was added, followed by a solution of (dibenzylideneacetone)dipalladium(0) (1.62 g, 1.77 mmol) and tri(2-furyl)-phosphine (820 mg, 3.53 mmol) in DMF (16 mL). After stirring at 70° C. for 16, the reaction mixture was partitioned between saturated aqueous ammonium chloride (200 mL) and diethyl ether (200 mL). The layers were separated, and the aqueous phase was extracted with diethyl ether (200 mL). The organic extracts were combined, dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography to afford a 54% yield (5.42 g) of 117a as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 8.29 (d, 1H, J=2.5 Hz), 7.70 (dd, 1H, J=8.5, 2.5 Hz), 7.35 (d, 1H, J=8.5 Hz), 4.37 (t, 2H, J=8.5 Hz), 3.91 (dd, 2H, J=8.5, 4.5 Hz), 3.73 (m, 1H), 1.46 (s, 9H); MS (ESI+) m/z 269.0 (M+H).

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