Methyl iodide → Benzyl 4-methoxy-2-(1-methoxycyclopropyl)pyrrolidine-1-carboxylate

HRID 81135Notes

Reaction equation

HRID 81135 reaction equation
[OH:1][C:2]1([CH:5]2[CH2:9][CH:8]([O:10][CH3:11])[CH2:7][N:6]2[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:4][CH2:3]1.[CH3:22]I.[H-].[Na+]>C1COCC1>[CH3:11][O:10][CH:8]1[CH2:7][N:6]([C:12]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13])[CH:5]([C:2]2([O:1][CH3:22])[CH2:3][CH2:4]2)[CH2:9]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86724493Benzyl 2-(1-hydroxycyclopropyl)-4-methoxypyrrolidine-1-carboxylate

Product 1

HCID 86724494Benzyl 4-methoxy-2-(1-methoxycyclopropyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of benzyl 2-(1-hydroxycyclopropyl)-4-methoxypyrrolidine-1-carboxylate (312 mg, 1.07 mmol) dissolved in THF (3.6 mL) at 0° C. was added methyl iodide (0.23 mL, 3.68 mmol) followed by sodium hydride (56.5 mg, 2.36 mmol). The mixture was stirred for 2 hours at room temperature. The reaction was quenched with ice, and diluted with diethyl ether. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-20% methanol/dichloromethane, linear gradient) to afford benzyl 4-methoxy-2-(1-methoxycyclopropyl)pyrrolidine-1-carboxylate. MS ESI calc'd. for C17H23NO4 [M+H]+ 306. found 306.

Workup

  1. customThe reaction was quenched with ice
  2. additiondiluted with diethyl ether
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (0-20% methanol/dichloromethane, linear gradient)

Sources & evidence

ORD record
ord-6f9abe76738a409d8b16bec992f79f2c
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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