2,3,5,6-Tetrafluorophenol → (S)-3-Benzyloxycarbonylamino-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid Tert-Butyl Ester

HRID 1091436Notes

Reaction equation

HRID 1091436 reaction equation
[F-].[K+].[C:3]([O:7][C:8](=[O:26])[CH2:9][C@H:10]([NH:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C:11](=[O:14])[CH2:12]Br)([CH3:6])([CH3:5])[CH3:4].[F:27][C:28]1[C:33]([F:34])=[CH:32][C:31]([F:35])=[C:30]([F:36])[C:29]=1[OH:37]>CN(C=O)C>[C:3]([O:7][C:8](=[O:26])[CH2:9][C@H:10]([NH:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C:11](=[O:14])[CH2:12][O:37][C:29]1[C:30]([F:36])=[C:31]([F:35])[CH:32]=[C:33]([F:34])[C:28]=1[F:27])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 698582,3,5,6-TetrafluorophenolHCID 522689Potassium FluorideHCID 7020820Z-Asp(OtBu)-bromomethylketone

Product 1

HCID 57725369(S)-3-Benzyloxycarbonylamino-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid Tert-Butyl EsterYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium fluoride (2.8 g) was added portionwise to a stirred solution of (S)-3-benzyloxycarbonylamino-5-bromo-4-oxo-pentanoic acid tert-butyl ester (18.6 g) and 2,3,5,6-tetrafluorophenol (9.3 g) in anhydrous DMF (250 mL) under nitrogen at room temperature. The mixture was then stirred for 18 hours before being quenched with ethyl acetate and water. The organic layer was removed and washed with sodium bicarbonate solution, dried (magnesium sulfate) and concentrated to give the sub-title product as an off-white solid (21.1 g, 96%). 1H NMR (400 MHz, CDCl3) δ 1.43 (9H, s), 2.76 (1H, dd), 3.06 (1H, dd), 4.67-4.71 (1H, m), 5.12 (1 h, d), 5.22 (1H, d), 5.86 (1H, d), 7.35-7.38 (5H, m) ppm; 19F NMR (376 MHz, CDCl3) (proton decoupled) δ −139.98, −140.00, −140.04, −140.06, −157.05, −157.07, −157.11, −157.13; MS ES (+) 486.23 (M+H).

Workup

  1. custombefore being quenched with ethyl acetate and water
  2. customThe organic layer was removed
  3. washwashed with sodium bicarbonate solution
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5879e6d163f04d2884899bd7485f2711
Source dataset
uspto-grants-2012_03
Patent number
US08129381B2

Reaction notes

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