Water → 2-Chloro-4-methoxyphenoxy-1,3-thiazole

HRID 404896

Reaction equation

HRID 404896 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[OH:10].C([O-])([O-])=O.[K+].[K+].Br[C:18]1[S:19][CH:20]=[CH:21][N:22]=1.O>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[O:10][C:18]1[S:19][CH:20]=[CH:21][N:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 764302-BromothiazoleHCID 874592-Chloro-4-methoxyphenol

Product 1

HCID 694346862-Chloro-4-methoxyphenoxy-1,3-thiazoleYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a suspension of 2-chloro-4-methoxyphenol (10 g, 63 mmol) and K2CO3 (9.7 g, 69.4 mmol) in N,N-dimethyl formamide (120 mL) was added 2-bromothiazole (11.4 g, 69.4 mmol). The suspension was heated at 150° C. for 4 hours, cooled to ambient temperature, and poured into water (1000 mL). The mixture was extracted with ether (2×300 mL) and the combined ether layers were dried (MgSO4), filtered and concentrated. The resulting black oil was purified by flash chromatography on silica gel eluting with a solvent gradient from 10% to 25% ethyl acetate in hexanes to provide 12.3 g of the title compound (81%) as a light yellow liquid. 1H NMR (300 MHz, DMSO-d6) δ ppm 3.81 (s, 3H) 7.01 (dd, J=9.01, 3.13 Hz, 1H) 7.18-7.21 (m, 1H) 7.23 (t, J=3.13 Hz, 2H) 7.47 (d, J=9.19 Hz, 1H); MS (ESI) m/z 241.9 (M+H)+.

Workup

  1. temperaturecooled to ambient temperature
  2. extractionThe mixture was extracted with ether (2×300 mL)
  3. dry with materialthe combined ether layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting black oil was purified by flash chromatography on silica gel eluting with a solvent gradient from 10% to 25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0030590b6e25478f8b085bb6eb5edfce
Source dataset
uspto-grants-2014_06
Patent number
US08748627B2

Linked notes

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