Methyl iodide → HCID 60067022, compound

HRID 2308098Notes

Reaction equation

HRID 2308098 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([O:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH2:13][C@H:12]1[CH2:21][OH:22])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[CH3:24]>CC(C)=O.[Ag]=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([O:16][Si:17]([CH3:18])([CH3:19])[CH3:20])[CH2:13][C@H:12]1[CH2:21][O:22][CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 6328Methyl iodideHCID 60067061HCID 60067061, compound

Product 1

HCID 60067022HCID 60067022, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 92152Silver(II) oxideCatalystHCID 180AcetoneSolvent

Conditions

Temperature
57 °C

Procedure

To (2S,4R)-2-Hydroxymethyl-4-trimethylsilanyloxy-pyrrolidine-1-carboxylic acid benzyl ester in 10 mL of acetone was added iodomethane 0.86 mL (13.5 mmol), silver oxide 3.04 g (13.2 mmol) and the solution was warmed to 57° C. for 8 h. The mixture was cooled to 25° C., filtered through celite and concentrated. The residue was taken up in 50 mL of EtOAc and was washed with Sat. NaHCO3 (2×50 mL). The organic layer dried over Na2SO4 and concentrated. The residue was loaded onto 50 mL silica and eluted with Hexane:EtOAc (3:7). The purified fraction were concentrated to give 0.66 g (67%) of (2S,4R)-2-Methoxymethyl-4-trimethylsilanyloxy-pyrrolidine-1-carboxylic acid benzyl ester as clear oil. HPLC: Rt 3.43 min. (98.2% area). 1H NMR (CDCl3, 300 MHz) δ: 7.38-7.32 (5H, m), 4.70 (2H, s), 4.56-4.46 (2H, m), 4.18-4.13 (2H, m), 3.86 (1H, q, J=5.5 Hz), 3.07-3.02 (1H, m), 1.99-1.95 (1H, m), 1.61 (3H, bs), 1.57-1.52 (1H, m), 0.12 (9H, s). LCMS (ESI) (M+H+) m/z: 338.2.

Workup

  1. temperatureThe mixture was cooled to 25° C.
  2. filtrationfiltered through celite
  3. concentrationconcentrated
  4. washwas washed with Sat. NaHCO3 (2×50 mL)
  5. dry with materialThe organic layer dried over Na2SO4
  6. concentrationconcentrated
  7. washeluted with Hexane:EtOAc (3:7)
  8. concentrationThe purified fraction were concentrated

Sources & evidence

ORD record
ord-410c316857184419b6a6f5ec9a86855a
Source dataset
uspto-grants-2004_12
Patent number
US06833456B2

Reaction notes

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