Lithium iodide → (S)-2-Iodomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1296177Notes

Reaction equation

HRID 1296177 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13]OS(C)(=O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[I-:19].[Li+]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][I:19])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 66321Lithium iodideHCID 10039261tert-butyl (2S)-2-[(methanesulfonyloxy)methyl]pyrrolidine-1-carboxylate2×

Product 1

HCID 11312942(S)-2-Iodomethyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 84.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
62 °C

Procedure

A solution of 2-(S)-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (compound (3) obtained from above, 30 g, 0.10 mol) in anhydrous tetrahydrofuran (600 mL) was cooled to 0° C. Lithium iodide (144 g, 1 mol) was added to the cold reaction mixture as a solid in portions while maintaining the reaction temperature at below 30° C. The reaction mixture was warmed to 62° C. until HPLC showed less than 2% starting material. The reaction mixture was quenched with 10% aqueous sodium thiosulfate (300 mL). Ethyl acetate (600 mL) was added to reaction mixture. The organic layer was separated. The aqueous layer was re-extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (2×100 mL), dried over MgSO4, filtered, and concentrated to leave an oily residual product (26.3 g, 78.6% yield). 1H NMR (CDCl3): δ 1.46 (d, 3H, CH3), 1.48 (d, 6H, 2×CH3), 1.792.14 (m, 4H, 2×CH2), 3.14–3.52 (m, 4H, 2×CH2) and 3.88 (m, 1H, CH); [M+H]+ at m/z 312.

Workup

  1. temperaturewhile maintaining the reaction temperature at below 30° C
  2. customThe reaction mixture was quenched with 10% aqueous sodium thiosulfate (300 mL)
  3. additionEthyl acetate (600 mL) was added to reaction mixture
  4. customThe organic layer was separated
  5. extractionThe aqueous layer was re-extracted with ethyl acetate (3×50 mL)
  6. washThe combined organic layer was washed with brine (2×100 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-3cf6f6c1c50f428f802880315db457ee
Source dataset
uspto-grants-2007_07
Patent number
US07244852B2

Reaction notes

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