Dimethylformamide → tert-butyl 5'-formyl-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Temperature

-78 °C

To a stirred solution of tert-butyl 5′-bromo-3′H-spiro[azetidine-3,1-isobenzofuran]-1-carboxylate (Intermediate 1, 2 g, 5.879 mmol, 1 eq) in dry THF (40 mL) was added n-BuLi (6.42 mL, 7.054 mmol, 1.2 eq) at −78° C. under nitrogen atmosphere. Reaction mixture was stirred for 10 minutes at −78° C. under nitrogen atmosphere. At −78° C., DMF (0.678 mL, 8.818 mmol, 1.5 eq) was added in drop wise manner over period of 10 minutes. Resulting reaction mixture was allowed to warm to −20° C. and stirred for 3 hours under nitrogen atmosphere. After complete consumption of starting material, reaction was quenched with 10% NH4Cl solution (5 mL) followed by water (70 mL) and extracted with ethyl acetate (3×30 mL). Combined organic phase was washed with brine solution (50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford title compound as pale yellow thick oil (1.5 g, crude). Crude compound was used as such for next reaction. (m/z): 290.1 (M+H).

1. customReaction mixture
2. customResulting
3. customreaction mixture
4. temperatureto warm to −20° C.
5. stirringstirred for 3 hours under nitrogen atmosphere
6. customAfter complete consumption of starting material, reaction
7. customwas quenched with 10% NH4Cl solution (5 mL)
8. extractionextracted with ethyl acetate (3×30 mL)
9. washCombined organic phase was washed with brine solution (50 mL)
10. dry with materialdried over anhydrous Na2SO4
11. concentrationconcentrated under reduced pressure

ORD record

ord-df0b1cedca3346bdbaa8938e290e1ae6

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221835B2