Sodium Iodide → N-[N-[(S)-3-[[(t-Butyloxy)carbonyl]amino]-2-oxobutyl]-L-phenylalanyl]-L-leucine, t-butyl ester

HRID 1981849Notes

Reaction equation

HRID 1981849 reaction equation
[NH2:1][C@H:2]([C:10]([NH:12][C@H:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH:15]([CH3:17])[CH3:16])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[CH2:26][C:27](=[O:38])[C@@H:28]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH3:29].[I-].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O>[C:33]([O:32][C:31]([NH:30][C@@H:28]([CH3:29])[C:27](=[O:38])[CH2:26][NH:1][C@H:2]([C:10]([NH:12][C@H:13]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:14][CH:15]([CH3:17])[CH3:16])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:37])([CH3:36])([CH3:34])[CH3:35]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 6352601H-Phe-Leu-OButHCID 13532962tert-butyl N-((2S)-4-chloro-3-oxobutan-2-yl)carbamate

Product 1

HCID 13633797N-[N-[(S)-3-[[(t-Butyloxy)carbonyl]amino]-2-oxobutyl]-L-phenylalanyl]-L-leucine, t-butyl esterYield 73.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of L-phenylalanyl-L-leucine, t-butyl ester (6 mmol) in 10 ml of dimethylformamide (under argon) was added a solution of [(S)-3-chloro-1-methyl-2-oxopropyl]carbamic acid, 1,1-dimethylethyl ester (1.33 g, 6 mmol) in 20 ml of dimethylformamide, followed by sodium iodide (450 mg, 3 mmol) and sodium bicarbonate (504 mg, 6 mmol). The reaction mixture was allowed to stir for 15 hours, and the solvent was then evaporated (<25° C., vacuum pump). The yellow residue was taken up into ethyl acetate (250 ml) and washed with water (4×25 ml) and brine (25 ml), then dried (sodium sulfate) and evaporated to a yellow residue (3.44 g). This was applied to a column of silica gel (Merck, 230-400 mesh, 250 g) and eluted with hexane-ethyl acetate (1.25:1). Fractions 25-40 (~30 ml each, homogeneous on TLC) were pooled and concentrated yielding 2.29 g of a colorless oil. Rapid recrystallization from ethyl acetate-hexane afforded 1.61 g of the title compound as a powdery white solid.

Workup

  1. customthe solvent was then evaporated (<25° C., vacuum pump)
  2. washwashed with water (4×25 ml) and brine (25 ml)
  3. dry with materialdried (sodium sulfate)
  4. customevaporated to a yellow residue (3.44 g)
  5. washeluted with hexane-ethyl acetate (1.25:1)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5a928d0264db4d6ca881a547d2e6768a
Source dataset
uspto-grants-1986_06
Patent number
US04594188

Reaction notes

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