2,3,5,6-Tetrafluorophenol → N-(1-methyl-3-isobutyl-indole-2-cabonyl)-valinyl-3-amino-4-oxo-5-(2,3,5,6-tetrafluorophenyloxy)-pentanoic acid, tert-butyl ester

HRID 2297053

Reaction equation

HRID 2297053 reaction equation
[F-].[K+].[CH3:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][CH:14]([CH3:16])[CH3:15])=[C:5]1[C:17]([NH:19][C@H:20]([C:24]([NH:26][CH:27]([C:36](=[O:39])[CH2:37]Br)[CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:25])[CH:21]([CH3:23])[CH3:22])=[O:18].[F:40][C:41]1[C:46]([F:47])=[CH:45][C:44]([F:48])=[C:43]([F:49])[C:42]=1[OH:50]>CN(C=O)C>[CH3:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][CH:14]([CH3:16])[CH3:15])=[C:5]1[C:17]([NH:19][C@H:20]([C:24]([NH:26][CH:27]([C:36](=[O:39])[CH2:37][O:50][C:42]1[C:43]([F:49])=[C:44]([F:48])[CH:45]=[C:46]([F:47])[C:41]=1[F:40])[CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:25])[CH:21]([CH3:23])[CH3:22])=[O:18].[CH3:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][CH:14]([CH3:16])[CH3:15])=[C:5]1[C:17]([NH:19][C@H:20]([C:24]([CH:28]([CH:27]([NH2:26])[C:36](=[O:39])[CH2:37][O:50][C:42]1[C:41]([F:40])=[C:46]([F:47])[CH:45]=[C:44]([F:48])[C:43]=1[F:49])[C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])=[O:25])[CH:21]([CH3:22])[CH3:23])=[O:18]

Participants

6

Reactant 3

HCID 698582,3,5,6-TetrafluorophenolHCID 522689Potassium FluorideHCID 86756359N-[(1-methyl-3-isobutyl-indole-2-cabonyl)valinyl]-3-amino-5-bromo-4-oxo-pentanoic acid, tert-butyl ester

Product 2

HCID 86756358N-[(1-methyl-3-isobutyl-indole-2-cabonyl)valinyl]-3-amino-4-oxo-5-(2,3,5,6-tetrafluorophenyloxy)-pentanoic acid, tert-butyl EsterHCID 131723666N-(1-methyl-3-isobutyl-indole-2-cabonyl)-valinyl-3-amino-4-oxo-5-(2,3,5,6-tetrafluorophenyloxy)-pentanoic acid, tert-butyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium fluoride (21.6 mg, 0.37 mmol) was added to a solution of N-[(1-methyl-3-isobutyl-indole-2-cabonyl)valinyl]-3-amino-5-bromo-4-oxo-pentanoic acid, tert-butyl ester (86.1 mg, 0.149 mmol) and 2,3,5, 6-tetrafluorophenol (27.0 mg, 0.163 mmol in DMF (2.0 ml). After stirring at room temperature for 3 hours, the reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was back-extracted with ethyl acetate. The organic layers were combined, washed with saturated NaHCO3 solution, and brine, dried over sodium sulfate, and concentrated. The residue was triturated with ether to give the titled product, N-(1-methyl-3-isobutyl-indole-2-cabonyl)-valinyl-3-amino-4-oxo-5-(2,3,5,6-tetrafluorophenyloxy)-pentanoic acid, tert-butyl ester as a white solid (43.8 mg, 44%). TLC (hexane/EtOAc, 50/50): Rf=0.50.

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate and water
  2. extractionThe aqueous layer was back-extracted with ethyl acetate
  3. washwashed with saturated NaHCO3 solution, and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-b8a4c2d1154744018ded014a58ca1e72
Source dataset
uspto-grants-2002_12
Patent number
US06489353B2

Linked notes

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