Trifluoroacetic acid → (4R)-4-{[5-(2-fluoroethoxy)-1-oxidopyridin-2-yl]methyl}-L-glutamic acid

HRID 591309Notes

Reaction equation

HRID 591309 reaction equation
C(OC([NH:8][C@H:9]([C:31]([O:33]C(C)(C)C)=[O:32])[CH2:10][C@H:11]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][F:29])=[CH:22][N+:21]=1[O-:30])[C:12]([O:14]C(C)(C)C)=[O:13])=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[F:29][CH2:28][CH2:27][O:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][C@H:11]([C:12]([OH:14])=[O:13])[CH2:10][C@@H:9]([C:31]([OH:33])=[O:32])[NH2:8])=[N+:21]([O-:30])[CH:22]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 117812666di-tert-Butyl (4R)-N-(tert-butoxycarbonyl)-4-{[5-(2-fluoroethoxy)-1-oxidopyridin-2-yl]methyl}-L-glutamate

Product 1

HCID 89155776(4R)-4-{[5-(2-fluoroethoxy)-1-oxidopyridin-2-yl]methyl}-L-glutamic acidYield 93.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 170 mg of di-tert-butyl (4R)—N-(tert-butoxycarbonyl)-4-{[5-(2-fluoroethoxy)-1-oxidopyridin-2-yl]methyl}-L-glutamate (0.32 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (124 μL, 5 eq) and the mixture was stirred for 2 h at room temperature. LC/MS revealed substantial quantities of starting material were present; hence an additional 5 eq of trifluoroacetic acid were added and stirring at room temperature was continued overnight. Repeated LC/MS still showed incomplete removal of the protecting groups. The mixture was evaporated, re-dissolved in trifluoroacetic acid and dichloromethane (2 mL each) and stirred at room temperature for another 2 h, whereupon the reaction was complete. The mixture was evaporated and the residue was purified by preparative HPLC (Method E), followed by lyophilisation to give 95 mg of the target compound as light brown lyophilisate in approx. 90% purity (84% purity adjusted yield).

Workup

  1. stirringstirring at room temperature
  2. waitwas continued overnight
  3. customRepeated LC/MS still showed incomplete removal of the protecting groups
  4. customThe mixture was evaporated
  5. dissolutionre-dissolved in trifluoroacetic acid
  6. stirringdichloromethane (2 mL each) and stirred at room temperature for another 2 h, whereupon the reaction
  7. customThe mixture was evaporated
  8. customthe residue was purified by preparative HPLC (Method E)

Sources & evidence

ORD record
ord-fc00b891e6f14a25b1dcbc17e5882e61
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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