Ethyl orthoformate → 5-(Trifluoromethyl)-1,3-benzothiazole

HRID 1182304Notes

Reaction equation

HRID 1182304 reaction equation
Cl.[NH2:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[SH:13].[CH2:14](OC(OCC)OCC)C>S(=O)(=O)(O)O.C(O)C>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[CH:5][C:4]2[S:13][CH:14]=[N:2][C:3]=2[CH:8]=1

Participants

5

Reactant 2

HCID 31214Ethyl orthoformateHCID 27346782-Amino-4-(trifluoromethyl)benzenethiol hydrochloride

Product 1

HCID 199372475-(Trifluoromethyl)-1,3-benzothiazoleYield 86%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of 5.1 g (22.2 mmol) of 2-amino-4-(trifluoromethyl) benzenethiol hydrochloride, 5.5 mL (33.3 mmol) of triethylorthoformate, and 2 drops of sulfuric acid was slowly heated to 180° C. over 1 h. The ethanol formed was allowed to escape via a short path distillation still. The reaction mixture was cooled to room temperature and the residue was dissolved in ethyl acetate, washed with saturated sodium bicarbonate, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography with ethyl acetate:hexane (1:9) to afford 3.8 g (86%) of 5-(trifluoromethyl)-1,3-benzothiazole as a solid. 1H-NMR (400 MHz, DMSO-d6): δ 9.58 (s, 1H), 8.44–8.42 (m, 2H), 7.80 (d, 1H).

Workup

  1. distillationto escape via a short path distillation still
  2. temperatureThe reaction mixture was cooled to room temperature
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washwashed with saturated sodium bicarbonate
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography with ethyl acetate:hexane (1:9)

Sources & evidence

ORD record
ord-f594e342b3fc439eaaa849d4d65f7dd1
Source dataset
uspto-grants-2007_10
Patent number
US07288541B2

Reaction notes

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