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

HRID 1852743Notes

Reaction equation

HRID 1852743 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 ES I 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-b822d3821873431ea7238975c69b0a81
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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