Sodium hydride → 6-[3-Butyl-5-([E]-styryl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

HRID 1514740Notes

Reaction equation

HRID 1514740 reaction equation
[H-].[Na+].[CH2:3]([C:7]1[C:11]([CH2:12][OH:13])=[C:10](/[CH:14]=[CH:15]/[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:9][N:8]=1)[CH2:4][CH2:5][CH3:6].Br[C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][N:24]=1>C1COCC1>[CH3:30][O:29][C:27](=[O:28])[C:26]1[CH:31]=[CH:32][C:23]([O:13][CH2:12][C:11]2[C:7]([CH2:3][CH2:4][CH2:5][CH3:6])=[N:8][O:9][C:10]=2/[CH:14]=[CH:15]/[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:24][CH:25]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 13349623Methyl 6-bromopyridine-3-carboxylateHCID 66644001[3-butyl-5([E]-styryl)-isoxazol-4-yl]-methanol

Product 1

HCID 667181516-[3-Butyl-5-([E]-styryl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl esterYield 77.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (170 mg, 4.24 mmol) in THF (7 mL) at 0° C. was added a solution of [3-butyl-5([E]-styryl)-isoxazol-4-yl]-methanol (993 mg, 3.86 mmol) in THF (17 mL) and the mixture was stirred for 30 min at room temperature. The reaction mixture was cooled to 5° C. and a solution of methyl 6-bromonicotinate (1.0 g, 4.6 mmol) in THF (17 mL) was added dropwise. The mixture was stirred at room temperature for 2 days, poured over ice and stirred for 5 min. The mixture was extracted twice with ethyl acetate, washed with brine, dried over sodium sulfate and concentrated to a yellow oily solid. The crude material was purified by flash chromatography (silica gel, heptane:ethyl acetate 1:0 to 3:2) to afford the title compound (1.17 g, 77%) as an orange semisolid. MS: m/e=393.2 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to 5° C.
  2. stirringThe mixture was stirred at room temperature for 2 days
  3. additionpoured over ice
  4. stirringstirred for 5 min
  5. extractionThe mixture was extracted twice with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated to a yellow oily solid
  9. customThe crude material was purified by flash chromatography (silica gel, heptane:ethyl acetate 1:0 to 3:2)

Sources & evidence

ORD record
ord-0352c3fe1575471aa0bbc9628fdc67f0
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

Loading…