Water → (S)-tert-Butyl 1-(dimethoxyphosphoryl)-2-oxohex-5-en-3-ylcarbamate

To a solution of dimethyl methylphosphonate (13.98 mL, 131 mmol) in THF (87 mL) at −78° C. was added n-BuLi (82 mL, 131 mmol) slowly. After completion of addition, the reaction was stirred for 40 min and then a solution of (S)-methyl 2-(tert-butoxycarbonylamino)pent-4-enoate (6.0 g, 26.2 mmol) in THF (30 mL) was added slowly. Stirring was continued for another 40 min at −78° C. The reaction mixture was then quenched by adding H2O (2.357 mL, 131 mmol). The reaction mixture was diluted with EtOAc (100 mL) and the layers were separated. The organic layer was washed with 1M HCl, saturated NaHCO3 solution followed by brine. The organic phase was then dried over MgSO4, filtered and concentrated to give a clear oil. The crude product was purified using silica gel chromatography to give 5E (7.46 g, 89%) as colorless oil. MS (ESI) m/z: 343.9 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 5.63-5.76 (1H, m), 5.08-5.17 (2H, m), 4.33-4.43 (1H, m), 3.80 (3H, d, J=2.20 Hz), 3.77 (3H, d, J=2.20 Hz), 3.28-3.37 (1H, m), 3.05-3.16 (1H, m), 2.58-2.69 (1H, m), 2.42 (1H, dt, J=14.58, 7.29 Hz), 1.43 (9H, s).

1. additionAfter completion of addition
2. stirringStirring
3. waitwas continued for another 40 min at −78° C
4. customThe reaction mixture was then quenched
5. customthe layers were separated
6. washThe organic layer was washed with 1M HCl, saturated NaHCO3 solution
7. dry with materialThe organic phase was then dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a clear oil
11. customThe crude product was purified

ORD record

ord-3629fc813e4e454d829c87c374a5135e

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409908B2