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

HRID 1050233Notes

Reaction equation

HRID 1050233 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]=[C:15]([O:25][C@H:26]4[CH2:35][O:34][C@H:33]5[C@@H:28]([O:29]C(C6C=CC=CC=6)[O:31][CH2:32]5)[CH2:27]4)[N:16](COCC[Si](C)(C)C)[C:11]3=[CH:10][C:9]=2[Cl:42])=[CH:4][CH:3]=1.C(O)=O.OS([O-])(=O)=O.[K+].[OH-].[Na+].[NH4+].[Cl-]>CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]=[C:15]([O:25][C@H:26]4[CH2:35][O:34][C@H:33]([CH2:32][OH:31])[C@@H:28]([OH:29])[CH2:27]4)[NH:16][C:11]3=[CH:10][C:9]=2[Cl:42])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 284Formic AcidHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 516920Potassium bisulfateHCID 900448115-(4-bromophenyl)-6-chloro-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 90044340(2R,3 S,5R)-5-((5-(4-bromophenyl)-6-chloro-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

5-(4-bromophenyl)-6-chloro-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 (1.5 g, 2.229 mmol) was dissolved in formic acid (30 ml, 782 mmol) and aqueous saturated KHSO4 (2 mL). The reaction was heated to 50° C. overnight, then diluted with EtOAc, followed by the addition of 3M NaOH until a pH of ˜13 was reached. After stirring 10 min at rt, saturated NH4Cl was added until a pH of ˜7 was reached. The aqueous phase was separated, and extracted with EtOAc (×2). The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by column chromatography on a Biotage™ 50 g column by eluting with 1% to 12% MeOH in CHCl3. LC-MS: calculated for C18H17BrClN3O4 453.01 observed m/e: 453.94 (M+H)+ (Rt 1.13/2 min).

Workup

  1. customThe aqueous phase was separated
  2. extractionextracted with EtOAc (×2)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by column chromatography on a Biotage™ 50 g column
  8. washby eluting with 1% to 12% MeOH in CHCl3
  9. custom453.94 (M+H)+ (Rt 1.13/2 min)

Sources & evidence

ORD record
ord-d4e785890a77433390d20bc1fa2a9b53
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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