Triethyl phosphite → Diethyl 3-(5-bromopyridin-2-yloxy)benzylphosphonate

HRID 1666371Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15]Cl)[CH:10]=2)=[N:6][CH:7]=1.[CH2:17]([O:19][P:20]([O:24]CC)[O:21][CH2:22][CH3:23])[CH3:18]>CCCCCCC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:10]=[C:11]([CH:12]=[CH:13][CH:14]=2)[CH2:15][P:20](=[O:24])([O:21][CH2:22][CH3:23])[O:19][CH2:17][CH3:18])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

5-Bromo-2-(3-(chloromethyl)phenoxy)pyridine (3.08 g, 10.3 mmol) from Step 2 was treated neat with triethylphosphite (2.65 mL, 15.5 mmol) and heated to 150° C. After 5 h, the reaction mixture was removed from the heating bath and treated slowly with heptane until an oil precipitated out of solution. Ethyl acetate was added until mixture became homogenous. Heptane was slowly added again (at a cooler temperature) until a white precipitate formed. After the addition of more heptane and stirring for 15 min, the precipitate was filtered to afford a white solid (3.35 g, 81% yield). MS (APCI) M+1=400.0; 1H NMR (400 MHz, CDCl3) δ ppm 1.26 (t, J=7.02 Hz, 6H) 3.17 (d, J=21.64 Hz, 2H) 3.98-4.08 (m, 4H) 6.84 (d, J=8.77 Hz, 1H) 7.00-7.05 (m, 1H) 7.08 (q, J=2.21 Hz, 1H) 7.15-7.20 (m, 1H) 7.35 (t, J=7.90 Hz, 1H) 7.77 (dd, J=8.58, 2.53 Hz, 1H) 8.21 (d, J=2.73 Hz, 1H).

Workup

customthe reaction mixture was removed from the heating bath
additiontreated slowly with heptane until an oil
customprecipitated out of solution
additionEthyl acetate was added until mixture
additionHeptane was slowly added again (at a cooler temperature) until a white precipitate
customformed
filtrationthe precipitate was filtered

Sources & evidence

ORD record: ord-5f26e7f4a24d44ea9d26168db142fb63
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044052B2

Reaction notes

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