Potassium Carbonate → [5-Fluoro-7-(methylsulfonyl)-2,3-dihydro-1,4-benzodioxin-2-YL]methanol

HRID 39002Notes

Reaction equation

HRID 39002 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:14])[C:5]2[O:10][CH2:9][CH:8]([CH2:11][OH:12])[O:7][C:6]=2[CH:13]=1.[CH3:15][S:16]([O-:18])=[O:17].[Na+].N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.[Cu]I>[F:14][C:4]1[C:5]2[O:10][CH2:9][CH:8]([CH2:11][OH:12])[O:7][C:6]=2[CH:13]=[C:2]([S:16]([CH3:15])(=[O:18])=[O:17])[CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 66878254(7-Bromo-5-fluoro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol

Product 1

HCID 66879117[5-Fluoro-7-(methylsulfonyl)-2,3-dihydro-1,4-benzodioxin-2-YL]methanolYield 33.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (7-bromo-5-fluoro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol (0.6 g, 2.3 mmol), sodium methanesulfinate (85%) (0.4 g, 3.5 mmol), CuI (0.04 g, 0.2 mmol), L-proline (0.05 g, 0.5 mmol) and K2CO3 (0.06 g, 0.5 mmol) in DMSO (6 ml) was heated in two batches under microwave radiation at 140° C. for 2 h in nitrogen-flushed vials. After cooling to ambient temperature, the batches were mixed, water and EtOAc were added and the water phase was extracted with EtOAc. The combined organic phases were washed with LiCl (5%), HCl (1 N), brine, dried (Na2SO4) and evaporated to dryness. The product was mixed with another batch of the same compound. Purification on flash column chromatography (isooctane/EtOAc/MeOH) gave the title compound (0.2 g). MS m/z (rel. intensity, 70 eV) 262 (M+, bp), 231 (32), 206 (12), 183 (17), 152 (14).

Workup

  1. customflushed vials
  2. temperatureAfter cooling to ambient temperature
  3. additionthe batches were mixed
  4. additionwater and EtOAc were added
  5. extractionthe water phase was extracted with EtOAc
  6. washThe combined organic phases were washed with LiCl (5%), HCl (1 N), brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated to dryness
  9. additionThe product was mixed with another batch of the same compound
  10. customPurification on flash column chromatography (isooctane/EtOAc/MeOH)

Sources & evidence

ORD record
ord-6878969fad5649249e4b9fb3af7831f1
Source dataset
uspto-grants-2013_09
Patent number
US08524766B2

Reaction notes

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