Hydrochloric Acid → Methyl 3-hydroxy-4-iodobenzoate

HRID 1871190Notes

Reaction equation

HRID 1871190 reaction equation
N[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[OH:12].Cl.N([O-])=O.[Na+].[I-:18].[K+]>O.CCOC(C)=O.C1COCC1>[OH:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[I:18])[C:6]([O:8][CH3:9])=[O:7]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 7020619Benzoic acid, 4-amino-3-hydroxy-, methyl esterHCID 23668193Sodium Nitrite

Product 1

HCID 10378812Methyl 3-hydroxy-4-iodobenzoateYield 73.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A cloudy, dark solution of the product from Step A (79 g, 0.47 mol), 3N HCl (750 mL), and THF (250 mL) was cooled to 0° C. A solution of NaNO2 (35.9 g, 0.52 mol) in 115 mL of water was added over ca. 5 minutes, and the solution was stirred for another 25 minutes. A solution of potassium iodide (312 g, 1.88 mol) in 235 mL of water was added all at once, and the reaction was stirred for an additional 15 minutes. The mixture was poured into EtOAc, shaken, and the layers were separated. The organic phase was washed with water and brine, dried (Na2SO4), and concentrated in vacuo to provide the crude product (148 g). Purification by column chromatography through silica gel (0%-50% EtOAc/hexane) provided the titled product (96 g, 73% yield).

Workup

  1. stirringwas stirred for an additional 15 minutes
  2. stirringshaken
  3. customthe layers were separated
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto provide the crude product (148 g)
  8. customPurification by column chromatography through silica gel (0%-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-e6a9fbe8f99a443f8c2121dcb5e8c5af
Source dataset
uspto-grants-2000_08
Patent number
US06103487

Reaction notes

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