Citric Acid → HCID 178497462, compound

HRID 1861051Notes

Reaction equation

HRID 1861051 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.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

9

Reactant 4

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

Product 1

HCID 178497462HCID 178497462, compoundYield 78%

Reagents, catalysts & solvents 4

HCID 807IodineCatalystHCID 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 (1.17 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 partitioned between ethyl acetate (150 mL) and water (100 mL). The organic material was washed with saturated sodium bicarbonate (80 mL) and brine (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%): 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 (s, 2H), 3.99 (s, 3H), 3.55 (s, 3H).

Workup

  1. additionadded in ˜5 portions (˜10 min)
  2. additionwas added
  3. customThe mixture was partitioned between ethyl acetate (150 mL) and water (100 mL)
  4. washThe organic material was washed with saturated sodium bicarbonate (80 mL) and brine (50 mL)
  5. dry with materialwere dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification
  8. customby crystallization from ethyl acetate (3 mL)

Sources & evidence

ORD record
ord-c0636bc7bb974e96961103b87ca5aa5e
Source dataset
uspto-grants-2003_03
Patent number
US06531491B1

Reaction notes

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