Tetrahydrofuran → 2-(4-Chloro-2,6-dimethyl-phenoxy)-4-(1-ethyl-2-methoxy-propylamino)-6-methyl-nicotinic acid methyl ester

HRID 1831661Notes

Reaction equation

HRID 1831661 reaction equation
[CH3:1][O:2][C:3](=[O:28])[C:4]1[C:9]([NH:10][CH:11]([CH2:15][CH3:16])[CH:12]([OH:14])[CH3:13])=[CH:8][C:7]([CH3:17])=[N:6][C:5]=1[O:18][C:19]1[C:24]([CH3:25])=[CH:23][C:22]([Cl:26])=[CH:21][C:20]=1[CH3:27].[H-].[Na+].[CH2:31]1COCC1>>[CH3:1][O:2][C:3](=[O:28])[C:4]1[C:9]([NH:10][CH:11]([CH2:15][CH3:16])[CH:12]([O:14][CH3:31])[CH3:13])=[CH:8][C:7]([CH3:17])=[N:6][C:5]=1[O:18][C:19]1[C:24]([CH3:25])=[CH:23][C:22]([Cl:26])=[CH:21][C:20]=1[CH3:27]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 695877062-(4-Chloro-2,6-dimethyl-phenoxy)-4-(1-ethyl-2-hydroxy-propylamino)-6-methyl-nicotinic acid methyl ester

Product 1

HCID 695873802-(4-Chloro-2,6-dimethyl-phenoxy)-4-(1-ethyl-2-methoxy-propylamino)-6-methyl-nicotinic acid methyl ester

Procedure

To a solution of 2-(4-chloro-2,6-dimethyl-phenoxy)-4-(1-ethyl-2-hydroxy-propylamino)-6-methyl-nicotinic acid methyl ester (50 mg, 0.123 mmol) in dry THF was added NaH and stirred for 20 min. An excess of Mel was added and the resulting mixture was stirred at rt overnight. The mixture cooled to rt and quenched with water and extracted with ethyl acetate. The organic layer was separated, washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to give an oil. The oil was purified through silica gel column chromatography using 20% ethyl acetate in hexane asan eluent to give the title compound as a clear oil. 1H NMR(CDCl3) d 8.20(d,1H), 7.00(s,2H), 6.14&6.10(two sets of s,1H), 3.859s,3H), 3.47(m,1H), 3.39&3.37(two sets of s,3H), 2.08(s,3H), 2.06(s,6H), 1.75(m,1H), 1.58(m,1H), 1.14(t,3H), 0.95(t,3H)ppm.

Workup

  1. additionAn excess of Mel was added
  2. stirringthe resulting mixture was stirred at rt overnight
  3. customquenched with water
  4. extractionextracted with ethyl acetate
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customto give an oil
  11. customThe oil was purified through silica gel column chromatography

Sources & evidence

ORD record
ord-533ff750bd594cf1a67d9f2f0beea1ff
Source dataset
uspto-grants-2006_06
Patent number
US07067664B1

Reaction notes

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