Azobisisobutyronitrile → Ethyl 5-(bromomethyl)-2-chloro-4-thiazolecarboxylate

HRID 1948339Notes

Reaction equation

HRID 1948339 reaction equation
[Cl:1][C:2]1[S:3][C:4]([CH3:12])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.C1C(=O)N([Br:20])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl>[Br:20][CH2:12][C:4]1[S:3][C:2]([Cl:1])=[N:6][C:5]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8]

Participants

5

Reactant 3

HCID 6547Azobisisobutyronitrile2×HCID 67184N-bromobutanimide2×HCID 53302340Ethyl 2-chloro-5-methyl-1,3-thiazole-4-carboxylate2×

Product 1

HCID 59406847Ethyl 5-(bromomethyl)-2-chloro-4-thiazolecarboxylateYield 31.1%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

Ethyl 2-chloro-5-methyl-1,3-thiazole-4-carboxylate (Intermediate 179, 2.8 g; 13.6 mmol) was dissolved in CCl4 (25 ml). NBS (2.3 g; 13 mmol) and AIBN (2.12 g; 13 mmol) were added in a single portion and the resultant reaction mixture was heated to reflux for 24 hours. Additional NBS (690 mg; 0.3 equiv.) and AIBN (636 mg; 0.3 mmol) were added to push the reaction to completion. Continued to heat for another 4 hours. Cooled to room temperature, filtered and concentrated the mother liquor. Redissolved in minimal DMSO (7 ml) and purified by Gilson HPLC (5-95% ACN/0.1% TFA; run time=35 min). Isolated 1.15 g of desired product in 29% yield MS (ES) MH+: 284, 286, 288 for C7H7BrClNO2S.

Workup

  1. customthe resultant reaction mixture
  2. temperaturewas heated
  3. temperatureto reflux for 24 hours
  4. customthe reaction to completion
  5. temperatureto heat for another 4 hours
  6. filtrationfiltered
  7. concentrationconcentrated the mother liquor
  8. dissolutionRedissolved in minimal DMSO (7 ml)
  9. custompurified by Gilson HPLC (5-95% ACN/0.1% TFA; run time=35 min)

Sources & evidence

ORD record
ord-1b941b323b594a929ef0043dff243904
Source dataset
uspto-grants-2013_03
Patent number
US08399489B2

Reaction notes

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