Citric Acid → HCID 178497462, compound

HRID 2181498Notes

Reaction equation

HRID 2181498 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:21]=[C:20]3[C:16]([CH:17]=[N:18][NH:19]3)=[CH:15][CH:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][O:11][CH3:12].[I:22]I.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.OS([O-])=O.[Na+]>O1CCOCC1.[OH-].[Na+].II.O.C(OCC)(=O)C.C(OCC)(=O)C.CCCCCC>[I:22][C:17]1[C:16]2[C:20](=[CH:21][C:13]([C:5]3[CH:6]=[CH:7][C:8]([O:9][CH2:10][O:11][CH3:12])=[C:3]([O:2][CH3:1])[CH:4]=3)=[CH:14][CH:15]=2)[NH:19][N:18]=1

Participants

11

Reactant 4

HCID 311Citric AcidHCID 807IodineHCID 218774636-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazoleHCID 23665763Sodium Bisulfite

Product 1

HCID 178497462HCID 178497462, compoundYield 77.6%

Reagents, catalysts & solvents 6

HCID 807IodineCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

In a 100-mL round-bottom flask under argon, 6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole (1.19 g, 4.18 mmol, 1 equiv) was dissolved in dioxane (25 mL) and 3N NaOH (14 mL). This mixture was treated with iodine (117 g, 14.60 mmol, 1.10 equiv) added in ˜5 portions (˜10 min). Several (˜4) additional portions of iodine (50 mg each) were added until the reaction was complete as visualized by TLC (3:7 ethyl acetate/hexane). The mixture was acidified with 20% citric acid (25 mL) and 5% NaHSO3 (20 mL) was added. The mixture was partioned between ethyl acetate (150 mL) and water (100 mL). Te organic material was washed with saturated sodium bicarbonate (80 ml) and bine (50 mL) and were dried over sodium sulfate and concentrated under reduced pressure. Purification by crystallization from ethyl acetate (3 mL) then hexane (7 ml) gave pure 3-iodo-6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole as a solid (1.33 g, 78 g): 1H NMR (CDCl3) δ 10.48 (bs, 1H), 7.62 (s, 1H), 7.57 (d, 1H, J=8.5 Hz), 7.47 (dd, 1H, J=1.3, 8.5 Hz), 7.18 (m, 3H), 5.29 (a, 2H), 3.99 (, 3H), 3.55 (s, 3H).

Workup

  1. additionadded in ˜5 portions (˜10 min)
  2. additionwas added
  3. washTe organic material was washed with saturated sodium bicarbonate (80 ml) and bine (50 mL)
  4. dry with materialwere dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification
  7. customby crystallization from ethyl acetate (3 mL)

Sources & evidence

ORD record
ord-11616425702b4a72a038d732ff9fb7e1
Source dataset
uspto-grants-2005_05
Patent number
US06891044B2

Reaction notes

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