Reaktion #434514

Reaktionsgleichung

5-bromo-2,4-dimethoxybenzaldehyde

thiophene-2-boronic acid

THF

KF

→

2,4-dimethoxy-5-thien-2-ylbenzaldehyde

Ausbeute 94.0%

Lösungsmittel

H2O

H2O

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigefitted with a reflux condenser, mechanical stirrer and nitrogen inlet adapter
2. 2
   SonstigeNitrogen was bubbled into the resulting solution for 20 min
3. 3
   Sonstigetransferred to a separatory funnel
4. 4
   Extraktionthe aqueous layer was extracted with EtOAc (100 mL)
5. 5
   FiltrationThe combined organic cuts were filtered through a pre-washed pad of solka floc (5 g)
6. 6
   Waschenwere washed with fresh EtOAc (200 mL)
7. 7
   EinengenThe resultant filtrate was concentrated to dryness
8. 8
   workup.DISSOLUTIONThe crude product was dissolved in THF (38 mL)
9. 9
   Sonstigecrystallized upon heptane (152 mL) addition
10. 10
    FiltrationThe product was filtered
11. 11
    Sonstigedried to a constant weight in the vacuum oven (38° C., 20 in Hg)

Vorschrift

Ex-1A: 5-bromo-2,4-dimethoxybenzaldehyde (20.3 g, 83 mmol), thiophene-2-boronic acid (11.6 g, 91 mmol) and THF (200 mL) were sequentially charged into a clean reaction vessel fitted with a reflux condenser, mechanical stirrer and nitrogen inlet adapter. Nitrogen was bubbled into the resulting solution for 20 min followed by the sequential addition of KF (10.1 g, 174 mmol), and Pd(tBu3P)2 (0.424 g, 0.83 mmol). The solution was immediately heated to 60° C. and aged for 1.5 h. The reaction was diluted with H2O (200 mL) and transferred to a separatory funnel containing EtOAc (200 mL) and H2O (200 mL). The layers were cut and the aqueous layer was extracted with EtOAc (100 mL). The combined organic cuts were filtered through a pre-washed pad of solka floc (5 g). The pad of solka floc and spent catalyst were washed with fresh EtOAc (200 mL) and this wash combined with the batch. The resultant filtrate was concentrated to dryness. The crude product was dissolved in THF (38 mL) and crystallized upon heptane (152 mL) addition. The product was filtered and then dried to a constant weight in the vacuum oven (38° C., 20 in Hg) affording 19.32 g (94%) of the desired 2,4-dimethoxy-5-thien-2-ylbenzaldehyde as a light off-white solid, mp 125–126° C. 1H-NMR (300 MHz, CDCl3): 10.34 (s, 1 H), 8.12 (s, 1 H), 7.44 (dd, 1 H, J=3.5 and 1.5 Hz), 7.31 (dd, 1 H, J=5.2 and 1.5 Hz), 7.07 (dd, 1 H, J=5.2 and 3.5 Hz), 6.51 (s, 1 H), 4.02 (s, 3 H), 3.99 (s, 3 H). HRMS (EI) Calcd. for C13H12O3S: 248.0507 (M+); Found: 248.0504.

Quelle