2-Methylthiazole → 5-(2-Methoxy-4-nitro-phenyl)-2-methyl-thiazole

HRID 1855503Notes

Reaction equation

HRID 1855503 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH3:12].C([O-])(=O)C.[K+].[CH3:18][C:19]1[S:20][CH:21]=[CH:22][N:23]=1>CN(C)C(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:12][O:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[C:21]1[S:20][C:19]([CH3:18])=[N:23][CH:22]=1

Participants

6

Reactant 3

HCID 771292-MethylthiazoleHCID 1012932-Bromo-5-nitroanisoleHCID 517044Potassium Acetate

Product 1

HCID 670963525-(2-Methoxy-4-nitro-phenyl)-2-methyl-thiazoleYield 42.6%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 31374DimethylacetamideSolvent

Procedure

In a microwave vial a mixture of 2-bromo-5-nitroanisole (800 mg, 3.38 mmol), potassium acetate (503 mg, 5.07 mmol) and tetrakis(triphenylphosphine)-palladium(0) (197 mg, 0.17 mmol) in N,N-dimethylacetamide (12 mL) were flushed with argon while 2-methylthiazole (1.71 g, 16.9 mmol) was added. The tube was sealed and the mixture irradiated two times for 30 minutes at 160° C. The red-brown mixture was partitioned between ethyl acetate and water. The water layer was re-extracted with ethyl acetate. The combined organic phases were washed three times with water, once with brine, dried with magnesium sulfate and evaporated to dryness. Column chromatography (70 g silica, heptane/ethyl acetate 7:3 v/v) afforded the title compound (360 mg, 42%) as a yellow solid. MS ISP (m/e): 251.1 [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=8.15 (s, 1H), 7.90 (dd, 1H), 7.84 (s, 1H), 7.72 (d, 1H), 4.05 (s, 3H), 2.76 (s, 3H). Mp 114-117° C.

Workup

  1. additionwas added
  2. customThe tube was sealed
  3. customthe mixture irradiated two times for 30 minutes at 160° C
  4. customThe red-brown mixture was partitioned between ethyl acetate and water
  5. extractionThe water layer was re-extracted with ethyl acetate
  6. washThe combined organic phases were washed three times with water
  7. dry with materialonce with brine, dried with magnesium sulfate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-59722fd22d2b444ca30c33e4a0d2bbe5
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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