Sodium Thiosulfate → 5-Fluoro-4-oxo-3-[(S)-2-(2-oxo-2H-pyridin-1-yl)-propionylamino]-pentanoic acid tert-butyl ester

HRID 2065486Notes

Reaction equation

HRID 2065486 reaction equation
[C:1]([O:5][C:6](=[O:25])[CH2:7][CH:8]([NH:13][C:14](=[O:24])[C@@H:15]([N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]1=[O:23])[CH3:16])[CH:9]([OH:12])[CH2:10][F:11])([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O.C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:25])[CH2:7][CH:8]([NH:13][C:14](=[O:24])[C@@H:15]([N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]1=[O:23])[CH3:16])[C:9](=[O:12])[CH2:10][F:11])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 666499995-Fluoro-4-hydroxy-3-[(S)-2-(2-oxo-2H-pyridin-1-yl)-propionylamino]-pentanoic acid tert-butyl ester

Product 1

HCID 865905065-Fluoro-4-oxo-3-[(S)-2-(2-oxo-2H-pyridin-1-yl)-propionylamino]-pentanoic acid tert-butyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of 5-Fluoro-4-hydroxy-3-[(S)-2-(2-oxo-2H-pyridin-1-yl)-propionylamino]-pentanoic acid tert-butyl ester (135 mg, 0.38 mmol) in anhydrous DCM (5 ml) was treated with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (193 mg, 0.46 mmol) at 0° C. The resulting mixture was kept at 0° C. for 1.5 h, diluted with ethyl acetate, then poured into a 1:1 mixture of saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium thiosulphate. The organic layer was removed and the aqueous layer re-extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (1% methanol in ethyl acetate) to afford the title compound as a colorless gum (125 mg, 93%): 1H NMR (400 MHz, CDCl3) δ 1.2-1.4 (9H, 2×s), 2.6-2.9 (2H, m), 4.7-4.9 (1H, m), 4.9-5.3 (2H, m), 5.6-5.7 (1H, m), 6.2-6.3 (1H, m), 6.5-6.6 (1H, m), 7.2-7.4 (1H, m), 7.5-7.6 (1H, m), 8.0-8.2 (1H, m); 13C NMR (100 MHz, CDCl3) δ 16.57, 16.87, 28.24, 28.29, 36.44, 36.60, 52.50, 52.62, 52.90, 53.09, 82.31, 82.44, 83.51, 83.72, 85.33, 85.55, 107.35, 107.44, 120.45, 120.49, 134.42, 134.67, 140.22, 140.36, 162.85, 162.98, 169.93, 169.99, 170.59, 170.63, 202.58, 202.64, 202.75, 202.80; 19F NMR (376 MHz, CDCl3) δ −231.94, −231.96, −232.48, −232.49.

Workup

  1. customThe organic layer was removed
  2. extractionthe aqueous layer re-extracted with ethyl acetate
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (1% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-9ea480ffa5314b729875467ef1a0b6ec
Source dataset
uspto-grants-2012_10
Patent number
US08288537B2

Reaction notes

Loading…