Tetrahydrofuran → Ethyl acetate methanol ammonium hydroxide

Temperature

65 °C

To 2-[4-(2-amino-2-oxoethoxy)phenyl]-6-benzyloxy-3-[3-methoxy-4-[(1-pyrrolidinyl)methyl]benzyl]benzo[b]thiophene (93 mg, 0.15 mmol) in THF (5 mL) was added lithium aluminum hydride (57 mg) at ambient temperature and the mixture was stirred under argon at 65° C. for 24 h. The reaction was quenched with water (1 mL) and sodium hydroxide solution (1.0 M, 1 mL) while stirring continued for 30 min. The mixture was then diluted with brine (50 mL) and extracted with dichloromethane (30 mL×3). The combined organic layers were dried with sodium sulfate and concentrated in vacuo. The crude reduction product was dissolved in THF (5 mL) and treated with a 25% aqueous solution of ammonium formate (2 mL) and palladium on carbon (10%, 100 mg) at ambient temperature under argon for 6 h before filtration through diatomaceous earth followed by rinsing with dichloromethane and methanol. The filtrate was extracted with dichloromethane (30 mL×3) which was washed with water (50 mL). The combined organic layers were dried with sodium sulfate and concentrated under reduced pressure. Chromatography with NH4OH:MeOH:EtOAc (3:7:90) afforded the product as a white solid (24 mg, 31%).

1. customThe reaction was quenched with water (1 mL) and sodium hydroxide solution (1.0 M, 1 mL)
2. stirringwhile stirring
3. waitcontinued for 30 min
4. additionThe mixture was then diluted with brine (50 mL)
5. extractionextracted with dichloromethane (30 mL×3)
6. dry with materialThe combined organic layers were dried with sodium sulfate
7. concentrationconcentrated in vacuo
8. dissolutionThe crude reduction product was dissolved in THF (5 mL)
9. additiontreated with a 25% aqueous solution of ammonium formate (2 mL) and palladium on carbon (10%, 100 mg) at ambient temperature under argon for 6 h before filtration through diatomaceous earth
10. washby rinsing with dichloromethane and methanol
11. extractionThe filtrate was extracted with dichloromethane (30 mL×3) which
12. washwas washed with water (50 mL)
13. dry with materialThe combined organic layers were dried with sodium sulfate
14. concentrationconcentrated under reduced pressure

ORD record

ord-ff3f54332f2c4b0594f8ac001e59ae68

Source dataset

uspto-grants-2000_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06025382