Diisopropylamine → HCID 66869283, compound

Temperature

-78 °C

A solution of EtOAc (16.1 ml, 164.48 mmol) in THF (250 ml) is slowly added under an atmosphere of argon at −78° C. to a solution of lithium diisopropylamine (prepared from 23.3 ml of diisopropylamine (164.48 mmol) and 102.8 ml of 1.6 M n-BuLi in hexane (164.48 mmol) in THF (250 ml). After stirring at −78° C. for 30 minutes, a solution of 2-chloro-7-methoxy-3,4-dihydro-2H-naphthalen-1-one (31.5 g, 149.53 mmol) in THF (250 ml) is slowly added during 30 minutes. The reaction mixture is stirred at −78° C. for 1 h. TLC analysis indicates complete conversion of starting material. A sat. aqueous solution of NH4Cl (250 ml) is carefully added to the reaction mixture at −78° C. The mixture is warmed to RT. The organic layer is separated, diluted with EtOAc and washed with brine. After drying over Na2SO4, the solvent is removed. Purification by FCC (hexane/EtOAc 4:1) yields the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.27 (t, J=9.4 Hz, 3H), 2.32-2.48 (m, 2H), 2.78-2.88 (m, 1H), 2.86-3.02 (m, 2H), 3.05-3.14 (m, 1H), 3.82 (s, 3H), 4.18 (q, J=9.4 Hz, 2H), 5.02-5.08 (m, 1H), 6.81-6.84 (m, 1H), 7.03 (d, J=10.5 Hz, 1H), 7.18-7.19 (m, 1H). ES+−MS: 281.3, 283.3 [M+H—H2O]+.

1. stirringThe reaction mixture is stirred at −78° C. for 1 h
2. temperatureThe mixture is warmed to RT
3. customThe organic layer is separated
4. additiondiluted with EtOAc
5. washwashed with brine
6. dry with materialAfter drying over Na2SO4
7. customthe solvent is removed
8. customPurification by FCC (hexane/EtOAc 4:1)

ORD record

ord-206d71876ef54da8a21f1985ca52fcf1

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07648989B2