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

HRID 967986Notes

Reaction equation

HRID 967986 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 as an 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 set 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-ed4536d090c6453a8575b1501af8e550
Source dataset
uspto-grants-2005_10
Patent number
US06956047B1

Reaction notes

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