Sodium Thiosulfate → (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

HRID 2422690Notes

Reaction equation

HRID 2422690 reaction equation
[C:1]([O:5][C:6](=[O:40])[CH2:7][C@H:8]([NH:23][C:24](=[O:39])[CH: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@H:9]([OH: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])([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: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:13]([F:21])=[C:14]([F:20])[CH:15]=[C:16]([F:19])[C:17]=1[F:18])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 86595207(S,S)-3-[2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyrylamino]-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester

Product 1

HCID 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 esterYield 85%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of (S,S)-3-[2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyrylamino]-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester (221 mg, 0.385 mmol) in anhydrous DCM (10 mL) was treated with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (212 mg, 0.5 mmol) at 0° C. The resulting mixture was kept at 0° C. for 2 hr, diluted with ethyl acetate, then poured into a 1:1 mixture of saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium thiosulfate. The organic layer was removed and the aqueous layer re-extracted with ethyl acetate. The combined organic extracts were dried (Magnesium sulfate) and concentrated. The residue was purified by flash chromatography (50-50% ethyl acetate/hexane) to afford the title compound as a white solid (187 mg, 85%); 1H NMR (400 MHz, CDCl3) δ 0.93 (3H, t), 1.36 (3H, s), 1.95 (1H, m), 2.21 (3H, s), 2.25 (1H, m), 2.73 (2H, dd), 2.89 (1H, dd), 4.91 (1H, m), 5.04-5.17 (2H, m), 5.47 (1H, m), 6.34 (1H, t), 6.80 (1H, m), 7.19 (1H, m), 7.68 (1H, d), 8.36-8.41 (2H, m).

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 (Magnesium sulfate)
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (50-50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-624cfdfe60d24e9fb9eb835944eba855
Source dataset
uspto-grants-2011_06
Patent number
US07960415B2

Reaction notes

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