4-(4-Methoxy-phenyl)-2-methyl-thiazole → 2-[7-(Tert-butyldimethylsilanyloxy)heptyl]-4-(4-methoxyphenyl)thiazole

HRID 1039148Notes

Reaction equation

HRID 1039148 reaction equation
C([Li])(C)(C)C.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]=[C:16]([CH3:19])[S:17][CH:18]=2)=[CH:10][CH:9]=1.Br[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]>O1CCCC1.[NH4+].[Cl-].[Cl-].[Na+].O>[Si:28]([O:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:19][C:16]1[S:17][CH:18]=[C:14]([C:11]2[CH:12]=[CH:13][C:8]([O:7][CH3:6])=[CH:9][CH:10]=2)[N:15]=1)([C:31]([CH3:32])([CH3:33])[CH3:34])([CH3:30])[CH3:29]

Participants

7

Reactant 3

HCID 7687654-(4-Methoxy-phenyl)-2-methyl-thiazoleHCID 4260352(6-Bromohexyloxy)-tert-butyldimethylsilaneHCID 178418306HCID 178418306, compound

Product 1

HCID 684899302-[7-(Tert-butyldimethylsilanyloxy)heptyl]-4-(4-methoxyphenyl)thiazoleYield 61.2%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Add a solution of tert-butyllithium (26.35 mmol, 15.5 mL, 1.7 M in hexanes) dropwise to a solution of 4-(4-methoxyphenyl)-2-methylthiazole (6.15 g, 29.9 mmol) in degassed anhydrous tetrahydrofuran (THF) (100 mL) at −78° C. under nitrogen and stir the solution for 45 minutes. To this solution, add a solution of (6-bromohexyloxy)-tert-butyldimethylsilane (7.20 g, 24.4 mmol) over 5 min and stir the mixture for 2 hours. Warm the mixture to 0° C., dilute with NH4Cl (200 mL) and brine (250 mL) and extract with methylene chloride (3×150 mL). Dry the combined organic extracts over magnesium sulfate and remove the solvent under reduced pressure. Purify the crude product by flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (5:1), to provide 2-[7-(tert-butyldimethylsilanyloxy)heptyl]-4-(4-methoxyphenyl)thiazole (6.27 g, 50%).

Workup

  1. stirringstir the mixture for 2 hours
  2. extractionextract with methylene chloride (3×150 mL)
  3. dry with materialDry the combined organic extracts over magnesium sulfate
  4. customremove the solvent under reduced pressure
  5. customPurify the crude product by flash column chromatography on silica gel
  6. washeluting with hexanes/ethyl acetate (5:1)

Sources & evidence

ORD record
ord-43b4714b1e834389a98d280abefa4705
Source dataset
uspto-grants-2013_10
Patent number
US08552039B2

Reaction notes

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