Sodium Iodide → (S)-iodomethyl 2-((tert-butoxycarbonyl)amino)-3-methylbutanoate

HRID 521605Notes

Reaction equation

HRID 521605 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:15]([CH3:17])[CH3:16])[C:10]([O:12][CH2:13]Cl)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Na+].[I-:19]>CC(C)=O.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:15]([CH3:17])[CH3:16])[C:10]([O:12][CH2:13][I:19])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 5238Sodium IodideHCID 54112037chloromethyl (2S)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoate

Product 1

HCID 88544124(S)-iodomethyl 2-((tert-butoxycarbonyl)amino)-3-methylbutanoateYield 49.4%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a solution of (S)-chloromethyl 2-((tert-butoxycarbonyl)amino)-3-methylbutanoate (4.53 g, 17 mmol) in acetone (50 mL) was added NaI (7.67 g, 51 mmol). The mixture was heated to reflux for 12 h. The solution was diluted with H2O (100 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel, eluted with PE:EA=100:1 to 50:1, to give (S)-iodomethyl 2-((tert-butoxycarbonyl)amino)-3-methylbutanoate (3 g, 49%) as a white solid. 1H NMR (400 MHz, CDCl3): δ ppm 6.06-6.05-7.30 (d, J=2.2, 1H), 5.86-5.85 (d, J=2.0, 1H), 4.97-4.95 (d, J=4.0, 1H), 4.25-4.22 (m, 1H), 2.20-2.18 (m, 1H), 1.46 (s, 9H), 1.01-1.00 (d, J=3.6, 3H), 0.94-0.93 (d, J=3.4, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 12 h
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography on silica gel
  8. washeluted with PE

Sources & evidence

ORD record
ord-6c33b420530446c4ba54bc211b66339d
Source dataset
uspto-grants-2016_05
Patent number
US09328119B2

Reaction notes

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