Trifluoroacetic acid → (S,S)-3-[2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyrylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid

HRID 2422691Notes

Reaction equation

HRID 2422691 reaction equation
C([O:5][C:6](=[O:40])[CH2:7][C@H:8]([NH:23][C:24](=[O:39])[C@@H:25]([N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([NH:34][C:35](=[O:37])[CH3:36])[C:29]1=[O:38])[CH2:26][CH3:27])[C:9](=[O:22])[CH2:10][O:11][C:12]1[C:17]([F:18])=[C:16]([F:19])[CH:15]=[C:14]([F:20])[C:13]=1[F:21])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[C:35]([NH:34][C:30]1[C:29](=[O:38])[N:28]([C@@H:25]([CH2:26][CH3:27])[C:24]([NH:23][C@H:8]([C:9](=[O:22])[CH2:10][O:11][C:12]2[C:17]([F:18])=[C:16]([F:19])[CH:15]=[C:14]([F:20])[C:13]=2[F:21])[CH2:7][C:6]([OH:40])=[O:5])=[O:39])[CH:33]=[CH:32][CH:31]=1)(=[O:37])[CH3:36]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 11592245(S,S)-3-[2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyrylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester

Product 1

HCID 11477827(S,S)-3-[2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyrylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acidYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S,S)-3-[2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyrylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester (187 mg, 0.327 mmol) in dichloromethane (5 mL) was cooled to 0° C. Trifluoroacetic acid (5 ml) was added and the resulting mixture allowed to warm to room temperature and stir for 2 hours. The mixture was then concentrated under reduced pressure and the residue redissolved in dichloromethane. This process was repeated several times in order to remove excess trifluoroacetic acid. The resulting solid was slurried in diethyl ether, filtered and washed with more diethyl ether. The solid was then dried to constant weight under vacuum. This gave the title product as a white solid (138 mg, 82%); 1H NMR (400 MHz, d6-DMSO) δ 0.78 (3H, t), 1.87-2.13 (5H, m), 2.56-2.78 (2H, m), 4.62 (1H, m), 5.18-5.29 (2H, m), 5.40 (1H, m), 6.28 (1H, t), 7.37 (1H, d), 7.53-7.66 (1H, m), 8.17-8.21 (1H, m), 8.92 (1H, d), 9.21 (1H, s), 12.51 (1H, br s); 19F NMR (376 MHz, d6-DMSO, proton-decoupled) δ−156.9, −141.1; M+H 516.2, M−H 514.2.

Workup

  1. concentrationThe mixture was then concentrated under reduced pressure
  2. dissolutionthe residue redissolved in dichloromethane
  3. customto remove excess trifluoroacetic acid
  4. filtrationfiltered
  5. washwashed with more diethyl ether
  6. customThe solid was then dried to constant weight under vacuum

Sources & evidence

ORD record
ord-99652b8c7ec945ac896d7240f883a4b5
Source dataset
uspto-grants-2011_06
Patent number
US07960415B2

Reaction notes

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