Trifluoroacetic acid → HCID 57516717, compound

HRID 1966564Notes

Reaction equation

HRID 1966564 reaction equation
O[CH:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([I:13])=[CH:9][N:8]=2)[C:5](=[O:14])[CH2:4][C:3]1([CH3:16])[CH3:15].FC(F)(F)C(OC(=O)C(F)(F)F)=O.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C(Cl)Cl>[I:13][C:10]1[CH:11]=[CH:12][C:7]([N:6]2[CH2:2][C:3]([CH3:15])([CH3:16])[CH2:4][C:5]2=[O:14])=[N:8][CH:9]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 9845Trifluoroacetic anhydrideHCID 12052TriethylsilaneHCID 58464056HCID 58464056, compound

Product 1

HCID 57516717HCID 57516717, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
22.5 °C

Procedure

(275 mg, 828 μmol) (5RS)-5-Hydroxy-1-(5-iodopyridin-2-yl)-4,4-dimethylpyrrolidin-2-one (Example 13, step 2) was dissolved in CH2Cl2 (2 ml) and trifluoroacetic anhydride (140 μl, 994 μmol, 1.2 equiv.) was added at room temperature. The mixture was stirred for 1 hr at 20-25° C. The solution was evaporated to dryness and the residue was dissolved in trifluoroacetic acid (957 μl, 12.4 mmol, 15 equiv.) and triethylsilane (159 μl, 994 μmol, 1.2 equiv.) was added at room temperature. The mixture was stirred 1 h at room temperature. The reaction mixture was evaporated and extracted with sat. NaHCO3 solution and two times with a small volume of dichloromethane. The crude product was purified by flash chromatography by directly loading the dichloromethane layers onto a silica gel column (20 gr, ethyl acetate/heptane gradient, 0:100 to 100:0). The desired 1-(5-iodopyridin-2-yl)-4,4-dimethylpyrrolidin-2-one (209 mg, 80% yield) was obtained as a white solid, MS: m/e=317.0 (M+H+).

Workup

  1. customThe solution was evaporated to dryness
  2. stirringThe mixture was stirred 1 h at room temperature
  3. customThe reaction mixture was evaporated
  4. extractionextracted with sat. NaHCO3 solution and two times with a small volume of dichloromethane
  5. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-895cf164ab334f58a56b51d1965ab7da
Source dataset
uspto-grants-2013_04
Patent number
US08420661B2

Reaction notes

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