Acetaldehyde → Isohexane ethyl acetate

To a stirred solution of (4R,9aR)-6-bromo-4-methyl-1,2,3,4,9,9a-hexahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (1.0 g) in dry tetrahydrofuran (30 mL) at −78° C. under argon was added dropwise a solution of butyl lithium in hexanes (2.5M, 1.2 mL). The mixture was stirred for 1 h then acetaldehyde (0.31 mL) was added dropwise. The mixture was warmed to room temperature, stirred for 30 minutes then partitioned between ethyl acetate (50 mL) and aqueous ammonium chloride solution (50 mL). The organic layer was washed (water), treated with di-tert-butyl dicarbonate (0.5 g), left to stand for 30 minutes then concentrated in vacuo. The residue was purified by flash column chromatography [SiO2; isohexane-ethyl acetate (9:1)→>(1:1)] to give (4R,9aR)-6-(1(RS)-ethanol)-iodo-4-methyl-1,2,3,4,9,9a-hexahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester as a clear oil (0.43 g), NMR δH (400 MHz, CDCl3) 7.13 (1H, dd, J 7.5, 1 Hz), 6.33 (1H, d, J 7.5 Hz), 4.69 (1H, q, J 6.5 Hz), 4.36 (1H, m), 4.29–3.81 (4H, m), 3.06 (1H, m), 3.01 (1H, dd, J8.5, 8.0 Hz), 2.66 (1H, m ), 2.51 (1H, dd, J 16, 6 Hz), 1.48 (9H, s), 1.44 (3H, d, J 6.5 Hz) and 1.24 (3H, dt, J 6.5, 4 Hz); m/z M+ 334 (M+1).

1. stirringstirred for 30 minutes
2. customthen partitioned between ethyl acetate (50 mL) and aqueous ammonium chloride solution (50 mL)
3. washThe organic layer was washed (water)
4. additiontreated with di-tert-butyl dicarbonate (0.5 g)
5. waitleft
6. waitto stand for 30 minutes
7. concentrationthen concentrated in vacuo
8. customThe residue was purified by flash column chromatography [SiO2

ORD record

ord-285767c48b0e4514b0d0920db13c6044

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07208494B2