Dimethylformamide → (+/-)-7-Chloro-3-hydroxy-5-propylisobenzofuran-1(3H)-one

Temperature

-78 °C

To a solution of 2-chloro-N,N-diethyl-4-propylbenzamide (1.82 g, 7.17 mmol) and N,N,N′N′-tetramethylethylenediamine (1.2 mL, 7.9 mmol) in 100 mL of anhydrous THF at −78° C. was added sec-butyllithium (7.9 mL of a 1.0 M solution in hexanes, 7.9 mmol). The reaction was stirred at −78° C. for 30 min and then there was added DMF (7.6 mL, 97.8 mmol). The reaction was stirred at −78° C. for 30 min and then was quenched with 1N HCl (10 mL). The reaction mixture was concentrated in vacuo. The residue was taken up in 6N HCl (40 mL) and stirred at 100° C. for 18 h. The reaction mixture was allowed to cool, was diluted with water and extracted with EtOAc. The organics were washed with brine, dried (MgSO4) and concentrated to afford a solid. This material was purified by acid-base extraction as follows. The solid was dissolved in 1:1 hexane/EtOAc and extracted twice with sat'd aq NaHCO3/sat'd aq Na2CO3. The organics were discarded. The combined aqueous extracts were acidified with 12 N HCl and extracted with EtOAc. The EtOAc extracts were washed with brine, dried (MgSO4), and concentrated to afford 0.66 g (41%) of the title compound as a tan powder. 1H NMR (CDCl3): δ 7.25 (s, 1H), 6.55 (s, 1H), 4.85 (broad s, 1H), 2.68 (t, 2H, J=7.7 Hz), 1.72-1.63 (m, 2H), 0.95 (t, 3H, J=7.4 Hz).

1. stirringThe reaction was stirred at −78° C. for 30 min
2. customwas quenched with 1N HCl (10 mL)
3. concentrationThe reaction mixture was concentrated in vacuo
4. stirringstirred at 100° C. for 18 h
5. temperatureto cool
6. additionwas diluted with water
7. extractionextracted with EtOAc
8. washThe organics were washed with brine
9. dry with materialdried (MgSO4)
10. concentrationconcentrated
11. customto afford a solid
12. customThis material was purified by acid-base extraction
13. dissolutionThe solid was dissolved in 1:1 hexane/EtOAc
14. extractionextracted twice with sat'd aq NaHCO3/
15. extractionextracted with EtOAc
16. washThe EtOAc extracts were washed with brine
17. dry with materialdried (MgSO4)
18. concentrationconcentrated

ORD record

ord-7ea17a1b49ff4937815c99aae141446a

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572805B2