Phosphorus oxychloride → HCID 86665690, compound

HRID 81045Notes

Reaction equation

HRID 81045 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-])[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)[C:7]=1[C:8]#[N:9].P(Cl)(Cl)([Cl:21])=O>>[Cl:21][C:3]1[C:2]([Cl:1])=[C:7]([C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)=[CH:5][N:4]=1)[C:8]#[N:9]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 669270323-Chloro-4-cyano-5-(3-methoxyphenyl)pyridine 1-oxide

Product 1

HCID 86665690HCID 86665690, compound

Procedure

A mixture of crude 3-chloro-4-cyano-5-(3-methoxyphenyl)pyridine 1-oxide from Step 2 and phosphorus oxychloride (15 mL) in a sealed tube was placed in a 100° C. bath. After 1 h at 100° C., HPLC analysis indicated that a 2:1 mixture of products was formed. The mixture was concentrated. Recrystallization from ethyl acetate/hexanes (10 mL/10 mL) gave 2,3-dichloro-5-(3-methoxyphenyl)isonicotinonitrile as white solid (200 mg). The mother liquor was purified by reverse phase HPLC, using Sunfire S10 30×250 mm column and eluting with 80-100% solvent B (90% methanol-10% water-0.1% TFA) in solvent A (10% methanol-90% water-0.1% TFA), to give additional 2,3-dichloro-5-(3-methoxyphenyl)isonicotinonitrile (400 mg). 1H NMR (500 MHz, methanol-d4) δ ppm 8.54 (1H, s), 7.45 (1H, t, J=7.97 Hz), 6.77-7.28 (3H, m), 3.86 (3H, s); MS (ES+) m/z: 279 (M+H); LC retention time: 3.768 min (analytical HPLC Method A). No attempt was made to isolate the undesired 2,5-dichloro-3-(3-methoxyphenyl)isonicotinonitrile isomer.

Workup

  1. customwas placed in a 100° C.
  2. additionHPLC analysis indicated that a 2:1 mixture of products
  3. customwas formed
  4. concentrationThe mixture was concentrated
  5. customRecrystallization from ethyl acetate/hexanes (10 mL/10 mL)

Sources & evidence

ORD record
ord-7dcd1692dbb1446b9f097ce080eb94c0
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

Loading…