Trifluoroacetic acid → 7-Bromo-2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one

HRID 1514234Notes

Reaction equation

HRID 1514234 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][CH2:13][CH2:14][NH:15][C:16]([O:18]C(C)(C)C)=O)=[C:6]([CH:11]=1)C(OC)=O.C(O)(C(F)(F)F)=O.C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:12][CH2:13][CH2:14][NH:15][C:16](=[O:18])[C:6]=2[CH:11]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 8471TriethylamineHCID 59403467Methyl 5-bromo-2-{[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]oxy}benzoate

Product 1

HCID 601249727-Bromo-2,3,4,5-tetrahydro-1,4-benzoxazepin-5-oneYield 58.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of methyl 5-bromo-2-{[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]oxy}benzoate (Preparation 70) (8.92 g, 23.8 mmmol) in DCM (18 ml) was treated with TFA (7 ml) and stirred for 5 hrs. Additional (2 ml) TFA was added and the reaction left overnight. The solvent was evaporated, re-evaporated with toluene (5×) and dissolved in toluene (50 ml). The resulting residue was treated with triethylamine (4 equiv) and heated at 100° C. overnight then evaporated. The residue was purified by flash chromatography twice eluting with 50% EtOAc/hexane then 40-45% EtOAc/hexane. The fractions were evaporated to give the title compound (3.4 g) as a white solid. MS (ES): C9H881BrNO2 requires 243; found 244 [M+H]+.

Workup

  1. waitthe reaction left overnight
  2. customThe solvent was evaporated
  3. customre-evaporated with toluene (5×)
  4. dissolutiondissolved in toluene (50 ml)
  5. customthen evaporated
  6. customThe residue was purified by flash chromatography
  7. washtwice eluting with 50% EtOAc/hexane
  8. customThe fractions were evaporated

Sources & evidence

ORD record
ord-255d8ad2c77f4ace8a44b2cb22b583d8
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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