N-Iodosuccinimide → Ethyl-4-iodo-5-(1-methylcyclopropyl)isoxazole-3-carboxylate

HRID 1506318Notes

Reaction equation

HRID 1506318 reaction equation
[CH3:1][C:2]1([C:5]2[O:9][N:8]=[C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:6]=2)[CH2:4][CH2:3]1.[I:15]N1C(=O)CCC1=O>C(O)(C(F)(F)F)=O>[CH2:13]([O:12][C:10]([C:7]1[C:6]([I:15])=[C:5]([C:2]2([CH3:1])[CH2:3][CH2:4]2)[O:9][N:8]=1)=[O:11])[CH3:14]

Participants

4

Reactant 2

HCID 120273N-IodosuccinimideHCID 67168649Ethyl 5-(1-methylcyclopropyl)isoxazole-3-carboxylate

Product 1

HCID 67168161Ethyl-4-iodo-5-(1-methylcyclopropyl)isoxazole-3-carboxylateYield 78.3%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A mixture of ethyl 5-(1-methylcyclopropyl)isoxazole-3-carboxylate (Preparation 4C, 1.5 g, 7.68 mmol) and 1-iodopyrrolidine-2,5-dione (2.07 g, 9.22 mmol) in TFA (25 mL) was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (50 mL) and washed sequentially with water (50 mL), 1N aqueous sodium hydroxide (50 mL), 2.5 M aqueous sodium bisulfate (50 mL), brine (50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give ethyl-4-iodo-5-(1-methylcyclopropyl)isoxazole-3-carboxylate (1.93 g, 75% yield) as a yellow liquid. The product had an HPLC ret. time=2.49 min. (condition B); LC/MS M+1=321.9; 1H NMR (400 MHz, CDCl3) δ ppm 0.85 (m, 2H), 1.12 (m, 2H), 1.40 (t, J=7.15 Hz, 3H), 1.42 (s, 3H), and 4.41 (q, J=7.15 Hz, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  3. washwashed sequentially with water (50 mL), 1N aqueous sodium hydroxide (50 mL), 2.5 M aqueous sodium bisulfate (50 mL), brine (50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-44b45a9a6c9d46e39c79812bef175955
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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