Hydrochloric Acid → Methyl 3-hydroxy-4-iodobenzoate

HRID 1421721Notes

Reaction equation

HRID 1421721 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-iodobenzoate

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 4-amino-3-hydroxybenzoate (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 title compound. 1H NMR (CDCl3, 400 MHz): d 7.75 (d, 1H, J=8.2 Hz, ArH); 7.62 (d, 1H, J=2.0 Hz, ArH); 7.33 (dd, 1H, J=8.2 and 2.0 Hz, ArH); 5.56 (s, 1H, OH) and 3.91 (s, 3H, OCH3).

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-44b1401ee77b4b2992451e21ae8cd02e
Source dataset
uspto-grants-2000_06
Patent number
US06077853

Reaction notes

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