Methyl iodide → Boc-L-Pro-Ome

HRID 1672373Notes

Reaction equation

HRID 1672373 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].O1CCC[CH2:17]1.C(=O)([O-])[O-].[K+].[K+].CI>>[N:8]1([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([O:12][CH3:17])=[O:11]

Participants

5

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-

Product 1

HCID 1277666Boc-L-Pro-OmeYield 97.1%

Procedure

N-(tert-Butoxycarbonyl)-L-proline (7.05 g, 0.0328 mol) was dissolved in THF (200 mL, 2 mol) and to this solution was added potassium carbonate (10.2 g, 0.0738 mol) and methyl iodide (5.0 mL, 0.08 mol). The resulting heterogeneous solution was heated to reflux for 16 h with vigorous stirring. The mixture was then filtered through a pad of diatomaceous earth and the filter pad was washed thoroughly with tetrahydrofuran (THF). The volatiles were removed in vacuo and the resulting residue was purified by CombiFlash chromatography using a 40 g column and eluting with EtOAc/hexanes (0-25%) to afford the desired product as a yellow oil (7.3 g, 97%). LC-MS: 130.2 (M−Boc+2H)+ and 252.1 (M+Na)+.

Workup

  1. temperatureThe resulting heterogeneous solution was heated
  2. temperatureto reflux for 16 h with vigorous stirring
  3. filtrationThe mixture was then filtered through a pad of diatomaceous earth
  4. washthe filter pad was washed thoroughly with tetrahydrofuran (THF)
  5. customThe volatiles were removed in vacuo
  6. customthe resulting residue was purified by CombiFlash chromatography
  7. washeluting with EtOAc/hexanes (0-25%)

Sources & evidence

ORD record
ord-7516636e82bb4d16876fb6f318012a01
Source dataset
uspto-grants-2011_08
Patent number
US07998959B2

Reaction notes

Loading…