2-Thiophenecarboxaldehyde → HCID 22340080, Verbindung

To a 2.0 M solution of LDA in THF/heptane/ethyl benzene (200 mL, 408 mmol) cooled by an ice/acetone bath, a 0.75 M solution of 2-phenoxypropionic acid (30.8 g, 185 mmol) in THF (250 mL) was added dropwise over 30 min, keeping the reaction temperature below −10° C. After allowing the reaction mixture to stir for 15 min, a 0.75 M solution of 2-thiophenecarboxaldehyde (20.8 g, 185 mmol) in THF (250 mL) was added dropwise over the course of 1 h, maintaining the reaction temperature below −5° C. After stirring for 5 min at 0° C., HPLC analysis showed the reaction to be complete. The reaction was poured into ice water (600 mL) and ether (500 mL) was added. Hexane (1.0 L) was added and the layers were separated. The aqueous layer was further extracted with Et2O: hexane (1:2) (750 mL). The organic layers were checked for product then discarded. ethyl acetate (500 mL) was added to the aqueous layer, acidified to pH=2 with conc. HCl (18 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×200 mL). The organic layer was dried over NaCl and solvent removed in vacuo to provide 50.0 g of crude product. The product was used in the next step without further purification: 1H NMR (400 MHz, CDCl3) δ 7.33 (dd, 1H), 7.26 (m, 2H), 7.12 (m, 1H), 7.04 (d, 1H), 6.97 (m, 2H), 6.87 (dd, 1H), 5.37 (s, 1H), 1.40 (s, 3H); MS (EI−) 277.1 (M−1)−.

1. customthe reaction temperature below −10° C
2. temperaturemaintaining the reaction temperature below −5° C
3. stirringAfter stirring for 5 min at 0° C.
4. customthe reaction
5. additionwas added
6. customthe layers were separated
7. extractionThe aqueous layer was further extracted with Et2O: hexane (1:2) (750 mL)
8. additionethyl acetate (500 mL) was added to the aqueous layer
9. customthe layers were separated
10. extractionThe aqueous layer was extracted with ethyl acetate (2×200 mL)
11. dry with materialThe organic layer was dried over NaCl and solvent
12. customremoved in vacuo

ORD-Eintrag

ord-ccda221537db45b993719928aa592042

Quelldatensatz

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06930120B2