Cesium carbonate → HCID 59649315, compound

HRID 1430998Notes

Reaction equation

HRID 1430998 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([O:10][CH:11]([CH3:13])[CH3:12])[CH:7]=[C:6]([OH:14])[CH:5]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:22][S:23]([C:26]1[CH:31]=[CH:30][C:29](F)=[CH:28][CH:27]=1)(=[O:25])=[O:24]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:5]=[C:6]([O:14][C:29]2[CH:30]=[CH:31][C:26]([S:23]([CH3:22])(=[O:25])=[O:24])=[CH:27][CH:28]=2)[CH:7]=[C:8]([O:10][CH:11]([CH3:12])[CH3:13])[CH:9]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 679941-Fluoro-4-(methylsulphonyl)benzeneHCID 23072925Methyl 3-hydroxy-5-isopropoxybenzoate

Product 1

HCID 59649315HCID 59649315, compoundYield 101.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of 3-hydroxy-5-isopropoxy-benzoic acid methyl ester (3.20 g, 15.2 mmol) in DMF (80 mL) was added Cs2CO3 (5.45 g, 16.7 mmol) and 4-fluorophenyl methyl sulfone (2.65 g, 15.2 mmol) at rt. The resulting mixture was heated at 115° C. for 12 hr. Then the mixture was concentrated. The resulting residue was partitioned between EtOAc and water. The aqueous layer was separated and extracted with EtOAc (2×). Combined organic layers were washed with water (1×), dried and concentrated to a residue, which was purified by silica gel flash chromatography (7.5×30 cm, hexane/EtOAc, v/v 5:1, 2:1, 1:1). Fractions containing the mono-alkylation product were pooled and concentrated to give 3-isopropoxy-5-(4-methanesulfonyl-phenoxy)-benzoic acid methyl ester (5.60 g, 100%) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 8.90 (d, J=9 Hz, 2H), 7.41 (m, 1H). 7.26 (m, 1H), 7.10 (d, J=9 Hz, 2H), 6.79 (m, 1H), 4.56-4.63 (m, 1H), 3.90 (s, 3H), 3.06 (s, 3H), 1.35 (d, J=6 Hz, 6H).

Workup

  1. concentrationThen the mixture was concentrated
  2. customThe resulting residue was partitioned between EtOAc and water
  3. customThe aqueous layer was separated
  4. extractionextracted with EtOAc (2×)
  5. washCombined organic layers were washed with water (1×)
  6. customdried
  7. concentrationconcentrated to a residue, which
  8. customwas purified by silica gel flash chromatography (7.5×30 cm, hexane/EtOAc, v/v 5:1, 2:1, 1:1)
  9. additionFractions containing the mono-alkylation product
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-1a92417b64494d72a013fd0fbce0d9d7
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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