Terephthalic acid monomethylester chloride → Methyl 4-(7-bromo-5-cyanobenzo[d]oxazol-2-yl)benzoate

HRID 2090084Notes

Reaction equation

HRID 2090084 reaction equation
[Cl-].[CH3:2][O:3][C:4](=[O:14])[C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1.[NH2:15][C:16]1[CH:17]=[C:18]([CH:21]=[C:22]([Br:25])[C:23]=1O)[C:19]#[N:20]>O1CCOCC1>[Br:25][C:22]1[C:23]2[O:11][C:9]([C:8]3[CH:7]=[CH:6][C:5]([C:4]([O:3][CH3:2])=[O:14])=[CH:13][CH:12]=3)=[N:15][C:16]=2[CH:17]=[C:18]([C:19]#[N:20])[CH:21]=1

Participants

4

Reactant 2

HCID 53442854Terephthalic acid monomethylester chlorideHCID 671407903-Amino-5-bromo-4-hydroxybenzonitrile

Product 1

HCID 68411439Methyl 4-(7-bromo-5-cyanobenzo[d]oxazol-2-yl)benzoateYield 89.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a 3-L round-bottom flask fitted with a stir bar and a Claisen adapter fitted with a thermocouple and a condenser blanketed with nitrogen was added terephthalic acid monomethyl ester chloride (37.3 g) and a solution of 3-amino-5-bromo-4-hydroxybenzonitrile (40 g, Step B) in dioxane (675 ml). The mixture was heated to reflux and stirred at this temperature overnight. The mixture was then cooled to room temperature and the dioxane was removed in vacuo. The flask was fitted with a Dean-Stark trap and p-toluenesulfonic acid monohydrate (35.8 g) and toluene (2.5 L) were added. The mixture was heated to reflux and stirred at this temperature overnight. The mixture was then allowed to cool, transferred to a new 5-L flask, and concentrated to a brown solid. The crude product was triturated with methanol to provide 55.5 g (83%) of the title compound. 1H NMR (500 MHz, DMSO-d6): δ 8.50 (s, 1H), 8.34 (d, J=8.0 Hz, 2H), 8.29 (s, 1H), 8.19 (d, J=8.0 Hz, 2H), 3.91 (s, 3H).

Workup

  1. customTo a 3-L round-bottom flask fitted with a stir bar
  2. customa Claisen adapter fitted with a thermocouple and a condenser
  3. temperatureThe mixture was heated
  4. temperatureto reflux
  5. customthe dioxane was removed in vacuo
  6. customThe flask was fitted with a Dean-Stark trap and p-toluenesulfonic acid monohydrate (35.8 g) and toluene (2.5 L)
  7. additionwere added
  8. temperatureThe mixture was heated
  9. temperatureto reflux
  10. stirringstirred at this temperature overnight
  11. temperatureto cool
  12. customtransferred to a new 5-L flask
  13. concentrationconcentrated to a brown solid
  14. customThe crude product was triturated with methanol

Sources & evidence

ORD record
ord-6cffcfeaa1e24abf8bea6d6d0e0f91f5
Source dataset
uspto-grants-2013_05
Patent number
US08436028B2

Reaction notes

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