Methyl iodide → (S)-4-Benzyl 1-methyl 2-((tert-butoxycarbonyl)amino)succinate

HRID 237193Notes

Reaction equation

HRID 237193 reaction equation
[NH:1]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:2]([C:14]([OH:16])=[O:15])[CH2:3][C:4](=[O:13])[O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:24]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[NH:1]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:2]([C:14]([O:16][CH3:24])=[O:15])[CH2:3][C:4](=[O:13])[O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 1581888N-tert-Butoxycarbonyl-L-aspartic acid beta-benzyl ester

Product 1

HCID 11393562(S)-4-Benzyl 1-methyl 2-((tert-butoxycarbonyl)amino)succinateYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Boc-Asp(OBn)-OH 2.4 g (1 equiv, 7.45 mmol) was dissolved in 17 mL of dry DMF in a 100 mL round-bottom flask. Finely ground K2CO3 (1.5 g, 11 mmol) was added to the solution to form a suspension. The mixture was cooled to 0° C. in an ice-bath over five minutes. MeI (1 mL, 15 mmol) was then added to the mixture over 20 seconds under a positive flow of nitrogen. A yellow color developed within 30 min. The resulting mixture was stirred for 3 hours. The ice-bath was removed and 25 mL of water were added and the mixture left standing at room temperature 2 hours. The mixture was then treated with 30 mL of water and extracted with 3×25 mL AcOEt. The organics were washed with saturated NaHCO3 1×, brine 3×, dried over Na2SO4 filtered and concentrated to yield a yellow oil. This material was passed through a short silica column (eluting w/ AcOEt), after concentration of the pure fractions 2.42 g of Boc-Asp(OBn)-OMe as a yellow oil was obtained (98% yield). 1H NMR (DMSO d6, 500 mHz): δ 7.36 (m, 5H), 5.10 (s, 2H), 4.40 (q, 1H), 3.6 (s, 3H), 2.80 (dd, 1H), 2.72 (dd, 1H), 1.38 (s, 9H). LCMS (C18, 2-98% CH3CN in 0.1% TFA/H2O over 6 min); Calculated mass for C17H23NO6 (M+H)+ 338.23. found by LC-MS 338.2.

Workup

  1. customto form a suspension
  2. customThe ice-bath was removed
  3. addition25 mL of water were added
  4. waitthe mixture left
  5. waitstanding at room temperature 2 hours
  6. additionThe mixture was then treated with 30 mL of water
  7. extractionextracted with 3×25 mL AcOEt
  8. washThe organics were washed with saturated NaHCO3 1×, brine 3×
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto yield a yellow oil
  13. washThis material was passed through a short silica column (eluting w/ AcOEt)

Sources & evidence

ORD record
ord-caa3fd91c5a5475497a9f3b7fc0dd6b5
Source dataset
uspto-grants-2014_02
Patent number
US08642544B2

Reaction notes

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