Methyl iodide → HCID 59468923, compound

HRID 1690114Notes

Reaction equation

HRID 1690114 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@:19]([CH2:32][OH:33])([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17]2)=[CH:12][C:11]=1[O:34][CH3:35].[CH3:36]I.[H-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[N:20]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[C@:19]([CH2:32][O:33][CH3:36])([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17]2)=[CH:12][C:11]=1[O:34][CH3:35]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59468952HCID 59468952, compound

Product 1

HCID 59468923HCID 59468923, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-5-[4-{[(2-fluorophenyl)methyl]oxy}-3-(methyloxy)phenyl]-2-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate (D62, 170 mg, 0.35 mmol) and methyl iodide (44 μl, 0.70 mmol) in dry DMF (2 ml) at 0° C. was added NaH (60% dispersion in mineral oil) (21 mg, 0.52 mmol) and the mixture was stirred for 1.5 h from 0° C. to r.t. The reaction was quenched with brine and extracted with ethyl acetate. The organic layer was washed three times with ice cold brine, dried (Na2SO4) and evaporated and the residue was purified by chromatography on silica gel using cyclohexane/ethyl acetate (1:0 to 85:15) to afford the title compound as a colourless oil (150 mg, 86%); Rt (HPLC): 6.62 min; MS: (ES/+) m/z: 526 [M+Na] C27H34FNO7 requires 503.

Workup

  1. customThe reaction was quenched with brine
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed three times with ice cold brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customthe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-f71ac630b6334a498974b97c27b5661d
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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