Potassium Iodide → HCID 86700897, compound

HRID 1424357Notes

Reaction equation

HRID 1424357 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:5]([CH:6]=O)=[C:4]([OH:12])[CH:3]=1.FC1[CH:21]=[C:20]([O:22]C)[CH:19]=C(O)C=1C=O.C(#N)C.[I-].[K+].C(=O)([O-])[O-].[Cs+].[Cs+].ClCC(=O)C>>[F:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:5]2[CH:6]=[C:19]([C:20](=[O:22])[CH3:21])[O:12][C:4]=2[CH:3]=1

Participants

7

Reactant 6

HCID 4875Potassium IodideHCID 6342AcetonitrileHCID 6571ChloroacetoneHCID 10796Cesium carbonate2×HCID 539444731427328-29-7HCID 86700898HCID 86700898, compound

Product 1

HCID 86700897HCID 86700897, compound

Procedure

To a solution of a mixture of 4-fluoro-2-hydroxy-6-methoxybenzaldehyde and 2-fluoro-6-hydroxy-4-methoxybenzaldehyde (Example 36A, 4.63 g, 27.2 mmol) in acetonitrile (49.7 mL, 952 mmol) was added potassium iodide (0.903 g, 5.44 mmol), cesium carbonate (9.75 g, 29.9 mmol) and 1-chloropropan-2-one (2.395 mL, 28.6 mmol). The mixture was stirred at r.t. for 2 h, was treated with 0.1 eq of cesium carbonate and heated to 60° C. for 1 h and 80° C. for another hour. The reaction was left overnight at r.t., then filtered over a small pad of silica and rinsed with ethyl acetate (approx 500 mL). The residue obtained after concentration was purified by silica gel chromatography (ISCO, 120 g of silica with 100% toluene using UV at 315 nm, then polarity was increased over time up to 10% ethyl acetate). The fractions were evaporated to give a 7:1 mixture of the desired/undesired isomers which was recrystallized overnight with ethyl acetate. The title material was obtained (216 mgs, 3.8%) as colorless crystals. LC (Method B): 1.928 min. LCMS (APCI) calcd for C11H10FO3 [M+H]+ m/z 209.06. found 209.1. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.55-7.61 (m, 1H), 6.78-6.99 (m, 1H), 6.46-6.53 (m, 1H), 3.96 (s, 3H), 2.55-2.60 (m, 3H).

Workup

  1. temperatureheated to 60° C. for 1 h and 80° C. for another hour
  2. waitThe reaction was left overnight at r.t.
  3. filtrationfiltered over a small pad of silica
  4. washrinsed with ethyl acetate (approx 500 mL)
  5. customThe residue obtained
  6. concentrationafter concentration
  7. customwas purified by silica gel chromatography (ISCO, 120 g of silica with 100% toluene using UV at 315 nm
  8. temperaturepolarity was increased over time up to 10% ethyl acetate)
  9. customThe fractions were evaporated
  10. customto give
  11. additiona 7:1 mixture of the desired/undesired isomers which
  12. customwas recrystallized overnight with ethyl acetate

Sources & evidence

ORD record
ord-273cd08e75e644d584b6040690b6cb83
Source dataset
uspto-grants-2015_01
Patent number
US08927688B2

Reaction notes

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