Sodium Carbonate → 2-Chloro-3-(1-ethylpropoxy)-6-(2-methoxy-4-trifluoromethoxyphenyl)-5-methylpyridine

HRID 1354237Notes

Reaction equation

HRID 1354237 reaction equation
[CH2:1]([CH:3]([O:6][C:7]1[CH:8]=[C:9]([CH3:27])[C:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][C:15]=2[O:25][CH3:26])=[N+:11]([O-])[CH:12]=1)[CH2:4][CH3:5])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].O=P(Cl)(Cl)[Cl:36]>>[Cl:36][C:12]1[C:7]([O:6][CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])=[CH:8][C:9]([CH3:27])=[C:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][C:15]=2[O:25][CH3:26])[N:11]=1

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 211048285-(1-Ethylpropoxy)-2-(2-methoxy-4-trifluoromethoxyphenyl)-3-methylpyridine-1-oxide

Product 1

HCID 211047772-Chloro-3-(1-ethylpropoxy)-6-(2-methoxy-4-trifluoromethoxyphenyl)-5-methylpyridine

Procedure

A solution of compound 44 (340 mg, 0.88 mmol) in POCl3 (0.4 ml) is stirred at 65° C. for 1 hour, then cooled to room temperature and poured onto ice (10 g). The resulting solution is neutralized with Na2CO3, and extracted with 50% EtOAc in hexane. The combined extracts are washed with water, brine, dried, filtered and evaporated. The crude product is purified by chromatography (eluted with 6% EtOAc in hexane) to give the product as a white crystalline solid. 1H NMR (CDCl3) δ 1.01 (t, J=7.6 Hz, 6H), 1.76 (m, 4H), 2.12 (s, 3H), 3.78 (s, 3H), 4.19 (m, 1H), 6.78 (s, 1H), 6.89 (dd, 1H), 7.05 (s, 1H), 7.26 (s, 1H), 7.27 (d, J=8.4 Hz, 1H). LCMS 404.27 (M+1).

Workup

  1. additionpoured onto ice (10 g)
  2. extractionextracted with 50% EtOAc in hexane
  3. washThe combined extracts are washed with water, brine
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product is purified by chromatography (eluted with 6% EtOAc in hexane)

Sources & evidence

ORD record
ord-1494b75971fd48ffb54c52bd4c2b466a
Source dataset
uspto-grants-2007_05
Patent number
US07223778B2

Reaction notes

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