Formic Acid → (2R,3S,5R)-5-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

HRID 1050231Notes

Reaction equation

HRID 1050231 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:11](COCC[Si](C)(C)C)[C:10]([O:20][C@H:21]3[CH2:30][O:29][C@H:28]4[C@@H:23]([O:24]C(C5C=CC=CC=5)[O:26][CH2:27]4)[CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1[I:8].C(O)=O.S([O-])(O)(=O)=O.[K+].[OH-].[Na+]>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:11][C:10]([O:20][C@H:21]3[CH2:30][O:29][C@H:28]([CH2:27][OH:26])[C@@H:23]([OH:24])[CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1[I:8]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 14798Sodium HydroxideHCID 516920Potassium bisulfateHCID 1234895916-chloro-5-iodo-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-imidazo[4,5-b]pyridine-

Product 1

HCID 90044277(2R,3S,5R)-5-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

6-chloro-5-iodo-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-imidazo[4,5-b]pyridine-(185 mg, 0.287 mmol) was dissolved in formic acid (1 ml, 26.1 mmol) and saturated potassium hydrogen sulfate (0.1 ml, 0.287 mmol). The reaction was heated to 50° C. for 4 h, and then diluted with EtOAc, followed by the addition of 3 M NaOH until pH 14 was reached. The reaction was stirred for 15 minutes at rt and the layers were separated. The aqueous layer was extracted with EtOAc (×2) and the combined EtOAc extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting crude product was purified by column chromatography on a Biotage™ 25 g column and eluted with 1% to 10% MeOH in DCM to yield the desired product. LC-MS: calculated for C12H13ClIN3O4 424.96 observed m/e: 426.00 (M+H)+ (Rt 1.05/2 min).

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with EtOAc (×2)
  3. washthe combined EtOAc extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting crude product was purified by column chromatography on a Biotage™ 25 g column
  8. washeluted with 1% to 10% MeOH in DCM

Sources & evidence

ORD record
ord-dc0bd28021a44c66b59dcbf624425534
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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