p-Toluenesulfonic acid → HCID 66998464, compound

HRID 2064775Notes

Reaction equation

HRID 2064775 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[CH:8][C:9]([F:16])=[C:10]2[O:14][CH:13](O)[CH2:12][C:11]=12)=[O:5])[CH3:2].C(OC(C1C=CC(F)=C2OC(OC)CC=12)=O)C.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[CH:8][C:9]([F:16])=[C:10]2[O:14][CH:13]=[CH:12][C:11]=12)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acid2×HCID 66998691HCID 66998691, compoundHCID 66998945HCID 66998945, compound

Product 1

HCID 66998464HCID 66998464, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A mixture of 7-fluoro-2-hydroxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester and 7-fluoro-2-methoxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester (1.15 g, see above) in toluene (6.0 mL) is added dropwise to a solution of PTSA (0.25 mmol) in toluene (5.0 mL) which is heated to reflux. Heating is continued for 5 h, an additional portion of PTSA (0.25 mmol) is added and the mixture is again heated to reflux for 7 h. The solvents are removed in vacuo and the residue is purified by flash chromatography (gradient: heptane to heptane/EtOAc 95/5) to give the desired product. 1H-NMR (CDCl3): δ=7.99 (dd, J=8.3 Hz, J=4.3 Hz, 1H); 7.78 (s, 1H); 7.44 (bs, 1H); 7.10 (t, J=9.3 Hz, 1H); 4.46 (q, J=7.0 Hz, 2H); 1.47 (t, J=7.0 Hz, 3H).

Workup

  1. temperatureis heated to reflux
  2. temperatureHeating
  3. temperaturethe mixture is again heated
  4. temperatureto reflux for 7 h
  5. customThe solvents are removed in vacuo
  6. customthe residue is purified by flash chromatography (gradient: heptane to heptane/EtOAc 95/5)

Sources & evidence

ORD record
ord-adb164565cfb49c0a4225cc103ab0c7f
Source dataset
uspto-grants-2012_10
Patent number
US08288435B2

Reaction notes

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