Ammonium Chloride → Bromo-(dimethoxy-phosphoryl)-acetic acid benzyl ester

Temperature

10 °C

To a solution of benzyl dimethyl phosphonoacetate (1.94 g, 7.5 mmol) in THF (15 mL) cooled to −78° C. in a dry ice/isopropanol bath was added LHMDS (9.0 mL of a 1 M solution in THF, 9.0 mmol). The reaction was allowed to warm to 10° C. over 30 min, then recooled to −78° C. NBS (1.6 g, 9.0 mmol) was added as a solution in THF (20 mL), and the reaction was allowed to warm to room temperature over 18 h. Saturated ammonium chloride was added to quench any remaining base, and the reaction was concentrated to dryness. Ethyl acetate was added, and the organic layer was washed with water and brine, and dried over sodium sulfate. The crude product was obtained as a yellow oil and was subsequently purified by flash column chromatography on silica gel eluting with 30% ethyl acetate in hexanes to afford the desired product, bromo-(dimethoxy-phosphoryl)-acetic acid benzyl ester, as a pale yellow oil, 1.61 g (63%). 1H NMR (300 MHz, CDCl3): δ 7.36 (m, 5H), 5.24 (s, 2H), 4.44 (d, J=14.1 Hz, 1H), 3.83 (q, J=4.8 Hz, 6H). LC-MS m/z=417 [C11H15O5P+H]+.

1. customrecooled to −78° C
2. temperatureto warm to room temperature over 18 h
3. customto quench any remaining base
4. concentrationthe reaction was concentrated to dryness
5. additionEthyl acetate was added
6. washthe organic layer was washed with water and brine
7. dry with materialdried over sodium sulfate
8. customThe crude product was obtained as a yellow oil
9. customwas subsequently purified by flash column chromatography on silica gel eluting with 30% ethyl acetate in hexanes

ORD record

ord-fb9c453fb0634e7aa767b5e260c7ffed

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08710236B2