Acetic Anhydride → 1-(4-Cyclopropyl-2-hydroxypyridin-3-yl)-3-(2-(trifluoromethyl) pyridin-4-yl) imidazolidin-2-one

HRID 572457Notes

Reaction equation

HRID 572457 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][N+:7]([O-])=[CH:6][C:5]=2[N:11]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=3)[C:12]2=[O:26])[CH2:3][CH2:2]1.C(OC(=O)C)(=[O:29])C>>[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([OH:29])[C:5]=2[N:11]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=3)[C:12]2=[O:26])[CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 710079694-Cyclopropyl-3-(2-oxo-3-(2-(trifluoromethyl) pyridin-4-yl)imidazolidin-1-yl) pyridine 1-oxide

Product 1

HCID 1785173291-(4-Cyclopropyl-2-hydroxypyridin-3-yl)-3-(2-(trifluoromethyl) pyridin-4-yl) imidazolidin-2-oneYield 8%

Procedure

4-Cyclopropyl-3-(2-oxo-3-(2-(trifluoromethyl) pyridin-4-yl)imidazolidin-1-yl)pyridine 1-oxide (I-50b: 100 mg, 0.273 mmol) was heated with acetic anhydride (5 mL) at 120° C. for 3 hours. The resulting mixture was concentrated, basified with dilute sodium bicarbonate solution, and diluted with DCM. The organic layer was dried over sodium sulphate and concentrated to afford the crude product. Purification by column chromatography on silica gel (3% methanol in chloroform), followed by preparative HPLC afforded 8 mg of the product (8% yield).

Workup

  1. concentrationThe resulting mixture was concentrated
  2. additiondiluted with DCM
  3. dry with materialThe organic layer was dried over sodium sulphate
  4. concentrationconcentrated
  5. customto afford the crude product
  6. customPurification by column chromatography on silica gel (3% methanol in chloroform)

Sources & evidence

ORD record
ord-f671a1b9a8ef4e40b31b26b2033be026
Source dataset
uspto-grants-2015_05
Patent number
US09029399B2

Reaction notes

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