Diisobutylaluminum hydride → [5-(3-Oxo-propyl)-tricyclo[8.2.1.03,8]trideca-3(8),4,6-trien-13-yl]-carbamic acid tert-butyl ester

Temperature

-78 °C

DIBAL-H (1M in toluene, 855 μl, 0.855 mmol) was added dropwise to a stirred solution of the product of Step 1 (290 mg, 0.777 mmol) in toluene (8 ml) maintaining the reaction temperature below −70° C. After stirring at −78° C. for 2 hours, more DIBAL-H (77 μl) was added and stirring was continued for 2 additional hours at −78° C. The mixture was quenched with methanol at −78° C., allowed to warm to room temperature and dispersed between ethyl acetate and 1N HCl. The organic phase was washed with sodium bicarbonate solution (sat), brine, dried and concentrated to give a colourless oil. Analysis by NMR showed ˜15% starting ester present, so the product was subjected to a further treatment with DIBAL-H (122 μl) for 2 hours at −78° C. as described above. The crude product was purified by column chromatography on silica gel eluting with 5:1 isohexane-ethyl acetate to give a colourless oil 149 mg (56%).1 NMR (CDCl3, 360 MHz) δ 9.81 (1H, s), 7.00 (1H, m), 6.90 (2H, m), 4.97 (1H, m), 4.04 (1H, m), 2.86–3.03 (4H, m), 2.75 (2H, m), 2.45–2.63 (4H, m), 1.71 (2H, m), 1.47 (9H, s), 1.19 (2H, m).

1. temperaturemaintaining the reaction temperature below −70° C
2. stirringstirring
3. customwas continued for 2 additional hours at −78° C
4. customThe mixture was quenched with methanol at −78° C.
5. temperatureto warm to room temperature
6. additiondispersed between ethyl acetate and 1N HCl
7. washThe organic phase was washed with sodium bicarbonate solution (sat), brine
8. customdried
9. concentrationconcentrated
10. customto give a colourless oil
11. customThe crude product was purified by column chromatography on silica gel eluting with 5:1 isohexane-ethyl acetate

ORD record

ord-3f91ba4db35f41e69fb2d627395ede17

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07138400B2