Lithium diisopropylamide → HCID 66671764, compound

Temperature

-60 °C

Stir a mixture of (R)-4-benzyl-3-pent-4-enoyl-oxazolidin-2-one (5.0 g, 19.3 mmol) and tetrahydrofuran (75 mL) in a 250 mL round bottom flask at −75° C. Transfer 2 M LDA (14.5 mL) to the flask via syringe and add at a rate such that the internal temperature does not reach above −60° C. After the addition is complete, allow the reaction to stir at −25° C. for 30 min then cool to about −60° C. At this point, add a solution of 2-bromomethyl-1,3-dichloro-5-methoxy-benzene (7.76 g, 28.96 mmol) in THF (25 mL). After the addition is complete, the reaction vessel is allowed to slowly warm up to 0° C., and maintain the internal reaction temperature at 0° C. for 4 hr. Quench the reaction with 30 mL aqueous 1N hydrochloric acid. Transfer the mixture to a 500 mL separatory funnel and dilute with 100 mL water and 100 mL ether. Separate the layers and extract the aqueous layer with ether. Dry the combined organic phase over anhydrous sodium sulfate, filter and concentrate to give a thick oil. Purify by silica gel chromatography using hexanes:ethyl acetate to obtain 6.65 g, (76%) of a pale yellow oil.

1. customdoes not reach above −60° C
2. additionAfter the addition
3. customthe reaction
4. stirringto stir at −25° C. for 30 min
5. additionAfter the addition
6. temperatureto slowly warm up to 0° C.
7. temperaturemaintain the internal reaction temperature at 0° C. for 4 hr
8. customQuench
9. customthe reaction with 30 mL aqueous 1N hydrochloric acid
10. customSeparate the layers
11. extractionextract the aqueous layer with ether
12. dry with materialDry the combined organic phase over anhydrous sodium sulfate
13. filtrationfilter
14. concentrationconcentrate
15. customto give a thick oil
16. customPurify by silica gel chromatography

ORD record

ord-43ae609dddb4481c80fb8302f1ccbba1

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153807B2