Methyl iodide → HCID 66995363, compound

HRID 2041904Notes

Reaction equation

HRID 2041904 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1([OH:20])[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10]1.[H-].[Na+].[CH3:23]I.[Cl-].[Li+]>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1([O:20][CH3:23])[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:10]1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 433294Lithium ChlorideHCID 65920453HCID 65920453, compound

Product 1

HCID 66995363HCID 66995363, compoundYield 95.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Tert-butyl 3-(2,3-difluorophenyl)-3-hydroxyazetidine-1-carboxylate (0.7 g, 2.45 mmol) was dissolved in N,N-dimethylformamide (20 mL) and sodium hydride (60% dispension in mineral oil, 0.2 g, 4.90 mmoL) was added at 0° C. The mixture was stirred at 0° C. for 15 min and at ambient temperature for 20 min after which methyliodide (0.41 mL, 2.94 mmol) was added. The mixture was stirred for 1 h at ambient temperature, a mixture of aqueous lithium chloride (5%, aq, 20 mL) and ethyl acetate (20 ml) was added and the organic phase was collected. The aqueous phase was extracted with ethyl acetate (2×20 mL) and the combined organic phase was dried (Na2SO4), filtered and evaporated. Purification by flash column chromatography on silica gel (ethyl acetate/isooctane 2:8 to 1:1) gave the title compound (0.7 g, 95%). MS m/z (rel. intensity, 70 eV) 299 (M+, 1), 223 (60), 198 (35), 169 (bp), 170 (bp).

Workup

  1. additionwas added
  2. additionwas added
  3. customthe organic phase was collected
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×20 mL)
  5. dry with materialthe combined organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by flash column chromatography on silica gel (ethyl acetate/isooctane 2:8 to 1:1)

Sources & evidence

ORD record
ord-baab6eb8c0f2431b9fa718c1200d2d29
Source dataset
uspto-grants-2013_11
Patent number
US08586572B2

Reaction notes

Loading…