Sodium Hydroxide → (2,2-Difluoro-1,3-dioxaindan-5-yl)methanol

HRID 57180Notes

Reaction equation

HRID 57180 reaction equation
[F:1][C:2]1([F:14])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11](O)=[O:12])=[CH:10][C:4]=2[O:3]1.COCCO[AlH2-]OCCOC.[Na+].[OH-].[Na+]>C1(C)C=CC=CC=1>[F:14][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([CH2:11][OH:12])=[CH:10][C:4]=2[O:3]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 6087722,2-Difluoro-1,3-benzodioxole-5-carboxylic acidHCID 16684438Red-Al

Product 1

HCID 12814281(2,2-Difluoro-1,3-dioxaindan-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

Commercially available 2,2-difluoro-1,3-benzodioxole-5-carboxylic acid (1.0 eq) is slurried in toluene (10 vol). Vitride® (2 eq) is added via addition funnel at a rate to maintain the temperature at 15-25° C. At the end of addition the temperature is increased to 40° C. for 2 h then 10% (w/w) aq. NaOH (4.0 eq) is carefully added via addition funnel maintaining the temperature at 40-50° C. After stirring for an additional 30 minutes, the layers are allowed to separate at 40° C. The organic phase is cooled to 20° C. then washed with water (2×1.5 vol), dried (Na2SO4), filtered, and concentrated to afford crude (2,2-difluoro-1,3-benzodioxol-5-yl)-methanol that is used directly in the next step.

Workup

  1. additionAt the end of addition the temperature
  2. temperatureis increased to 40° C. for 2 h
  3. temperaturemaintaining the temperature at 40-50° C
  4. customto separate at 40° C
  5. temperatureThe organic phase is cooled to 20° C.
  6. washthen washed with water (2×1.5 vol)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-5371fb249df742b0934ad1106937ebe3
Source dataset
uspto-grants-2016_09
Patent number
US09434717B2

Reaction notes

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