beta-Methyl vinyl phosphate (MAP)

Description

A chemical compound.

Uses

Meropenem intermediate. A 1β-methyl carbapenem derivative as antibacterial agent.

Synthesis

General procedure for the synthesis of the compound (CAS: 93711-81-0) from 4-β-methylazabicyclohexyl ketone ester (X) and diphenyl chlorophosphate: a solution of 4-β-methylazabicyclohexyl ketone ester (X) was cooled in an ice bath to -10 to -15 °C, and diisopropylethylamine (14.57 g, 0.113 mol) and diphenyl chlorophosphate were added sequentially, protected by nitrogen gas (27.54 g, 0.102 mol). The reaction mixture was kept stirred at the same temperature for 5 hours until the complete disappearance of compound (X) was confirmed by TLC detection. At the end of the reaction, a large number of white crystals were precipitated from the reaction mixture, after which petroleum ether (300 mL) and 3.5% aqueous sodium dihydrogen phosphate (300 mL) were added to the mixture and the crystals were washed by stirring. After filtration, the filter cake was washed with petroleum ether (100 mL) and water (500 mL) in turn, and after drying, the target product PNB (4R,5S,6S)-3-(diphenoxy)phosphoryloxy-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid ester (XI) (49.3 g, yield : 81%; purity: 98%). The physicochemical properties of the product were as follows: [α]D25 = +40~+44° (c = 0.5, methanol); melting point: 125-126°C; IR (KBr) νmax cm-1 : 1780, 1745, 1605; 1H NMR (CDCl3) δ: 1.24 (3H, d), 1.35 (3H, d), 2.38 (1H, d, J = 3.2 Hz), 3.35 (1H, dd), 3.52 (1H, m), 4.26 (1H, dd), 4.30 (1H, m), 5.24-5.41 (2H, ABq), 7.29 (10H, m), 7.58 and 8.18 (2H, d).

storage

-20°C Freezer, Under Inert Atmosphere

References

[1] Patent: WO2007/104219, 2007, A1. Location in patent: Page/Page column 15
[2] Journal of Organic Chemistry, 1992, vol. 57, # 15, p. 4243 - 4249
[3] Journal of Antibiotics, 1998, vol. 51, # 8, p. 757 - 770
[4] Patent: WO2007/31858, 2007, A2. Location in patent: Page/Page column 13
[5] Patent: EP2014666, 2009, A1. Location in patent: Page/Page column 10