Pyridine → (2S)-2-(((tert-butoxy)carbonyl)amino)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)propanoic acid

HRID 1726757Notes

Reaction equation

HRID 1726757 reaction equation
FC(F)(F)C(OC1C(OC(=O)C(F)(F)F)=C(I)C=CC=1)=O.[CH3:22][C:23]([CH3:37])([O:25][C:26]([NH:28][C@H:29]([C:34]([OH:36])=[O:35])[CH2:30]C(=O)N)=[O:27])[CH3:24].[N:38]1C=CC=CC=1.C(=O)([O-])O.[Na+].[CH:49]1[C:61]2[CH:60]([CH2:62][O:63][C:64](ON3C(=O)CCC3=O)=[O:65])[C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[C:53]=2[CH:52]=[CH:51][CH:50]=1>CN(C)C=O.O>[CH3:37][C:23]([CH3:22])([O:25][C:26]([NH:28][C@H:29]([C:34]([OH:36])=[O:35])[CH2:30][NH:38][C:64]([O:63][CH2:62][CH:60]1[C:61]2[CH:49]=[CH:50][CH:51]=[CH:52][C:53]=2[C:54]2[C:59]1=[CH:58][CH:57]=[CH:56][CH:55]=2)=[O:65])=[O:27])[CH3:24]

Participants

7

Reactant 5

HCID 1049PyridineHCID 82035N2-((tert-Butoxy)carbonyl)-L-asparagineHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium BicarbonateHCID 12041285Bistrifluoroacetoxyiodobenzene

Product 1

HCID 7019527(2S)-2-(((tert-butoxy)carbonyl)amino)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)propanoic acidYield 88%

Reagents, catalysts & solvents 1

HCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Procedure

Bis(trifluoroacetoxy)iodobenzene (44.4 g, 103.2 mmol) was added to a solution of N-[(1,1-dimethylethoxy)carbonyl]-L-asparagine (Boc-Asn; 20.00 g, 86.1 mmol) in N,N-dimethylformamide/water (2:1; 300 mL). The solution was stirred at room temperature for 30 min and then pyridine (10 mL, 123.6 mmol) was added. The solution was stirred at room temperature for 4.5 h and then the solvent was evaporated (45° C., ˜0.5 mm Hg). The residue was dissolved in acetone/water (1:1; 400 mL) and sodium hydrogen carbonate (31.8 g, 378.5 mmol) and 1-[[(9H-fluoren-9-ylmethoxy)carbonyl]oxy]-2,5-pyrrolidinedione (Fmoc-Osu; 34.74 g, 103.0 mmol) were added. The mixture was stirred at room temperature overnight, then the acetone was evaporated and the mixture was acidified to pH 1 with 1 M HCl and extracted with ethyl acetate (200 mL, then 100 mL). The combined organic layers were washed with brine (3×50 mL), dried (Na2SO4), filtered, evaporated (45° C., ˜0.5 mm Hg), and chromatographed (50-60% ethyl acetate/hexanes) to give N-[(1,1-dimethylethoxy)carbonyl]-3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine (32.33 g, 88%) as a white solid.

Workup

  1. stirringThe solution was stirred at room temperature for 4.5 h
  2. customthe solvent was evaporated (45° C., ˜0.5 mm Hg)
  3. dissolutionThe residue was dissolved in acetone/water (1:1; 400 mL)
  4. stirringThe mixture was stirred at room temperature overnight
  5. customthe acetone was evaporated
  6. extractionextracted with ethyl acetate (200 mL
  7. washThe combined organic layers were washed with brine (3×50 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated (45° C., ˜0.5 mm Hg)
  11. customchromatographed (50-60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-78a09b8880a64e1e876ff990c3717183
Source dataset
uspto-grants-2009_02
Patent number
US07491741B2

Reaction notes

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