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 (5)-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 finally purified using silica gel chromatography to give the desired product (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) ppm.

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 finally purified

ORD record

ord-6600fe42cba24f46bf482f71c97ed0f7

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901115B2