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

HRID 1947864Notes

Reaction equation

HRID 1947864 reaction equation
C(OC([N:8]([C:16]1[CH:21]=[CH:20][C:19]([CH2:22]Br)=[CH:18][C:17]=1[Br:24])C(OC(C)(C)C)=O)=O)(C)(C)C.[P:25]([O:32]CC)([O:29][CH2:30][CH3:31])[O:26][CH2:27][CH3:28]>>[NH2:8][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][P:25](=[O:32])([O:29][CH2:30][CH3:31])[O:26][CH2:27][CH3:28])=[CH:18][C:17]=1[Br:24]

Participants

3

Reactant 2

HCID 31215Triethyl phosphiteHCID 67255008HCID 67255008, compound2×

Product 1

HCID 86654008Phosphonic acid, P-[(4-amino-3-bromophenyl)methyl]-, diethyl ester

Conditions

Temperature
120 °C

Procedure

Di-tert-butyl[2-bromo-4-(bromomethyl)phenyl]imidodicarbonate (Compound 108B, 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 on an Isco Combiflash 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=2.27 Hz, 1H), 7.04 (ddd, J=2.27, 2.40, 8.21 Hz, 1H), 6.71 (dd, J=0.76, 8.08 Hz, 1H), 3.97-4.06 (m, 4H), 2.96-3.04 (m, 2H), 1.26 (t, J=7.07 Hz, 6H); MS (ES+): m/z: 322.00, 323.96 [MH+]. HPLC: tR=2.83 min (UPLC TOF MS: polar—3 min).

Workup

  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 on an Isco Combiflash
  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

Sources & evidence

ORD record
ord-b908a60a8c134d6ba6dcc2739ca2bd7f
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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