(S)-2-tert-butoxycarbonylamino-3-(9H-fluoren-9-ylmethoxycarbonylamino)propionic acid methyl ester → 3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester

HRID 1352068Notes

Reaction equation

HRID 1352068 reaction equation
CC(C)(OC([NH:7][C@H:8]([C:28]([O:30][CH3:31])=[O:29])[CH2:9][NH:10][C:11]([O:13][CH2:14][CH:15]1[C:27]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])=O)C>FC(F)(F)C(O)=O.ClCCl>[CH:17]1[C:16]2[CH:15]([CH2:14][O:13][C:11]([NH:10][CH2:9][C@@H:8]([C:28]([O:30][CH3:31])=[O:29])[NH2:7])=[O:12])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]=2[CH:20]=[CH:19][CH:18]=1

Participants

3

Reactant 1

HCID 59977282(S)-2-tert-butoxycarbonylamino-3-(9H-fluoren-9-ylmethoxycarbonylamino)propionic acid methyl ester

Product 1

HCID 695121003-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of N-[(1,1-dimethylethoxy)carbonyl]-3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester (Example 62; 200 mg, 0.45 mmol) in trifluoroacetic acid/dichloromethane (1:1; 2 mL) was stirred at room temperature for 40 min. The solvent was evaporated and ethyl acetate (10 mL) was added. The solution was washed with saturated aqueous sodium hydrogen carbonate, dried (Na2SO4), filtered and evaporated to give 3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester. HOAT (73 mg, 0.45 mmol), DCC (111 mg, 0.45 mmol), 2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]-benzoic acid (Example 36; 148 mg, 0.45 mmol) and N,N-dimethylformamide (5 mL) were added and the solution was stirred at room temperature for 1.5 h. Water was added and the solution was extracted three times with ethyl acetate. The combined extracts were washed with brine, dried (Na2SO4), filtered, evaporated, and chromatographed (40–80% ethyl acetate/hexanes) to give 3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine, methyl ester (116 mg, 40%).

Workup

  1. customThe solvent was evaporated
  2. additionethyl acetate (10 mL) was added
  3. washThe solution was washed with saturated aqueous sodium hydrogen carbonate
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-0144d59eb26e4713914aa20d40796d21
Source dataset
uspto-grants-2007_05
Patent number
US07217728B2

Reaction notes

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