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Phosphonic acid, (2-cyclohexyl-2-oxoethyl)-, dimethyl ester synthesis
- Product Name:Phosphonic acid, (2-cyclohexyl-2-oxoethyl)-, dimethyl ester
- CAS Number:58009-66-8
- Molecular formula:C10H19O4P
- Molecular Weight:234.23
Yield:58009-66-8 97%
Reaction Conditions:
Stage #1: dimethyl methane phosphonatewith n-butyllithium in tetrahydrofuran at -78; for 0.5 h;
Stage #2: methyl cyclohexylcarboxylate in tetrahydrofuran at -78 - 0; for 1.5 h;
Steps:
86.1 Step 1: Preparation of Dimethyl (2-cyclohexyl-2-oxoethyl)phosphonate:
At about -78 C, to a solution of dimethyl methylphophonate (34.92 g, 281.69 mmol) in dry THF (150 ml) was added n-BuLi solution (116 mL, 281.69 mmol) 2.5 M in THF dropwise. The reaction mass was allowed to stir at about -78 °C for about 30 minutes and then a solution of compound methyl cyclohexanecarboxylate in THF (50 mL) was added to reaction mixture at same temperature. The resulting mixture was kept stirring at about -78 °C for about 30 minutes and then slowly warmed up to about 0 °C in about lhour. After completion, reaction mass was quenched by the addition of water ( 150 mL) and the mixture was extracted with ethyl acetate (2 x 200 mL). Combined organic layer was evaporated under reduced pressure to give compound Dimethyl (2- cyclohexyl-2-oxoethyl)phosphonate (32 g, 97%) as clear thick liquid. χΗΝΜΡν (CDCI3, 400 MHz) δ: 3.74 (s, 3H), 3.71 (s. 3H), 3.10 (s, 1H), 3.04 (s, 1H), 2.52-2.49 (m, 1H), 1.85-1.82 (m, 2H), 1.74-1.71 (m, 2H), 1.63-1.60 (m, 2H), 1.29-1.20 (m, 4H); Mass (LCMS): 235 (M + 1).
References:
WO2017/134555,2017,A1 Location in patent:Page/Page column 100; 101