Methyl iodide → HCID 67404226, compound

HRID 1188184Notes

Reaction equation

HRID 1188184 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=2)([OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:25].[Cl-].[NH4+]>O1CCCC1>[F:20][C:18]1[CH:19]=[C:14]([C:10]2([O:13][CH3:25])[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]2)[CH:15]=[C:16]([F:21])[CH:17]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 67403681HCID 67403681, compound

Product 1

HCID 67404226HCID 67404226, compoundYield 66.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl-3-(3,5-difluorophenyl)-3-hydroxypyrrolidin-1-carboxylate (3.8 g, 12.7 mmol) in dry tetrahydrofuran (50 mL), was added sodium hydride (60% dispersion in mineral oil, 0.76 g, 19 mmol). The mixture was stirred for 10 min after which iodomethane (1.58 mL, 25.4 mmol) was added. The mixture was stirred for 15 min, aqueous saturated ammonium chloride solution (50 ml) was added and the aqueous phase was extracted with ethyl acetate (2×50 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated. Purification by flash column chromatography on silica gel (ethyl acetate/isooctane, 1:9 to 1:1) gave the title compound (2.64 g, 66%). MS m/z (rel. intensity, 70 eV) 257 (31), 240 (17), 212 (13), 127 (18), 57 (bp).

Workup

  1. additionwas added
  2. extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customPurification by flash column chromatography on silica gel (ethyl acetate/isooctane, 1:9 to 1:1)

Sources & evidence

ORD record
ord-06765c531fef4b6495076f8eba1de044
Source dataset
uspto-grants-2014_03
Patent number
US08673962B2

Reaction notes

Loading…