Diisopropylamine → HCID 15086681, compound

To a solution of dry diisopropylamine (3.3 mL, 24 mM) in dry tetrahydrofuran (25 mL) at -78° C., was added dropwise a 2.3N solution of n-butyllithium in hexane (10.4 mL, 24 mM). After the reaction solution was stirred for 15 minutes, a solution of 2,2,5-trimethyl-3(2H)-furanone (2.0 g, 16 mM) in tetrahydrofuran (10 mL) was added dropwise. Hexamethylphosphoramide (4.4 mL, 24 mM) was the added dropwise for 30 minutes. Finally, p-bromobenzaldehyde (3.6 g, 19.2 mM) in tetrahydrofuran (10 mL) was added in one portion. The reaction solution was stirred 10 minutes when trifluoroacetic anhydride (5.6 mL, 40 mM) was added in one portion. Again, the reaction solution was stirred for 15 minutes when triethylamine (5.9 mL, 47.6 mM) was added and was allowed to room temperature. The reaction mixture was then partitioned between saturated aqueous sodium chloride (50 mL) and diethyl ether (50 mL). The layers were separated. The organic layers were then washed with saturated aqueous sodium chloride (2×25 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give dark liquid. After the crude product was dissolved in dichloromethane (100 mL), trifluoroacetic anhydride (5.6 mL, 40 mM) was added. After thirty minutes, triethylamine (2.75 mL, 20 mM) was added. The resulting mixture was stirred for one hour, washed with 1N aqueous hydrochloric acid, dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford an amber oil. The crude oil was purified by chromatography (silica gel, petroleum ether-ethyl acetate) to give yellow-brown crystals (1.8 g, 39%). Recrystallization from hexane gave an analytically pure product, m.p. 109°-110° C.

1. additionadded dropwise for 30 minutes
2. additionwas added in one portion
3. additionwas added
4. customwas allowed to room temperature
5. customThe reaction mixture was then partitioned between saturated aqueous sodium chloride (50 mL) and diethyl ether (50 mL)
6. customThe layers were separated
7. washThe organic layers were then washed with saturated aqueous sodium chloride (2×25 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto give dark liquid
12. waitAfter thirty minutes
13. stirringThe resulting mixture was stirred for one hour
14. washwashed with 1N aqueous hydrochloric acid
15. dry with materialdried over magnesium sulfate
16. filtrationfiltered
17. concentrationconcentrated under reduced pressure
18. customto afford an amber oil
19. customThe crude oil was purified by chromatography (silica gel, petroleum ether-ethyl acetate)

ORD record

ord-7ac0029e73ee40958aa9c762cf08932d

Source dataset

uspto-grants-1991_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05017601