Cesium carbonate → 4-(3-Chloro-4-methanesulfonyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl ester

HRID 1177119Notes

Reaction equation

HRID 1177119 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[S:9]([CH3:12])(=[O:11])=[O:10].[CH3:13][O:14][C:15]([C:17]1[CH:27]=[C:26]([OH:28])[C:20]2[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=2[CH:18]=1)=[O:16].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:13][O:14][C:15]([C:17]1[CH:27]=[C:26]([O:28][C:6]2[CH:5]=[CH:4][C:3]([S:9]([CH3:12])(=[O:11])=[O:10])=[C:2]([Cl:1])[CH:7]=2)[C:20]2[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=2[CH:18]=1)=[O:16]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 25067323Methyl 4-hydroxy-2,2-dimethyl-2,3-dihydro-1-benzofuran-6-carboxylateHCID 591699402-Chloro-4-fluoro-1-(methylsulfonyl)benzene

Product 1

HCID 595604364-(3-Chloro-4-methanesulfonyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-chloro-4-fluoro-1-(methylsulfonyl)benzene (939 mg, 4.50 mmol), 4-hydroxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl ester (3e) (1.00 g, 4.50 mmol) and Cs2CO3 (2.93 g, 9.00 mmol) in DMF (5 mL) was heated to 80° C. for 1.5 h, cooled to room temperature, quenched with H2O and extracted with 3× EtOAc. The organic layers were washed with 2×H2O, dried over Na2SO4 and concentrated. The residue was purified by Biotage column chromatography with 25-50% EtOAc in hexanes to give a white solid (1.70 g, 92% yield). 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J=8.84 Hz, 1 H) 7.31 (d, J=1.26 Hz, 1 H) 7.25 (d, J=1.26 Hz, 1 H) 7.10 (d, J=2.27 Hz, 1 H) 6.88-7.03 (m, 1 H) 3.89 (s, 3H) 3.28 (s, 3 H) 2.88 (s, 2 H) 1.50 (s, 6 H); LCMS for C19H19ClO6S m/z 411.00 and 413.00 (M+H)+.

Workup

  1. temperaturecooled to room temperature
  2. customquenched with H2O
  3. extractionextracted with 3× EtOAc
  4. washThe organic layers were washed with 2×H2O
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by Biotage column chromatography with 25-50% EtOAc in hexanes

Sources & evidence

ORD record
ord-21ed1c51fced492eb3f2b1417abfe28c
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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