Triethyl phosphite → Phosphonic acid, P-[(4-amino-3-bromophenyl)methyl]-, diethyl ester

Temperature

120 °C

Di-tert-butyl [2-bromo-4-(bromomethyl)phenyl]imidodicarbonate (Compound 32E, 6.0 g, 13 mmol) was taken up in triethyl phosphite (5.0 mL, 29 mmol) and stirred at 120° C. for 16 h. The reaction mixture was transferred to a microwave vial and was irradiated in the microwave for 4 h at 190° C. The reaction mixture was concentrated in vacuo. The compound was purified by flash column chromatography eluting with 10 to 100% EtOAc in heptane. The product was partitioned between EtOAc and water and separated. The aqueous was extracted with EtOAc (3×) and the combined organic fractions were washed with brine, dried over sodium sulfate, filtered, and concentrated to afford the title compound. 1H NMR (400 MHz, chloroform-d) δ 7.33 (t, J=2.3 Hz, 1H), 7.04 (ddd, J=2.3, 2.4, 8.2 Hz, 1H), 6.71 (dd, J=0.8, 8.1 Hz, 1H), 3.97-4.06 (m, 4H), 2.96-3.04 (m, 2H), 1.26 (t, J=7.1 Hz, 6H); MS (ESI): m/z: 322.00, 323.96 [M+H]+. UPLC: tR=2.83 min (UPLC-TOF: polar—3 min).

1. customwas irradiated in the microwave for 4 h at 190° C
2. concentrationThe reaction mixture was concentrated in vacuo
3. customThe compound was purified by flash column chromatography
4. washeluting with 10 to 100% EtOAc in heptane
5. customThe product was partitioned between EtOAc and water
6. customseparated
7. extractionThe aqueous was extracted with EtOAc (3×)
8. washthe combined organic fractions were washed with brine
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-7faf05e51662467eb45843c5a88d0dad

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133224B2