Water → 5-(Chloromethyl)-2,2-difluorobenzo[d][1,3]dioxole

HRID 1773104Notes

Reaction equation

HRID 1773104 reaction equation
[F:1][C:2]1([F:13])[O:6][C:5]2[CH:7]=[CH:8][C:9]([CH2:11]O)=[CH:10][C:4]=2[O:3]1.O=S(Cl)[Cl:16].O>CC(OC)(C)C.CN(C1C=CN=CC=1)C>[Cl:16][CH2:11][C:9]1[CH:8]=[CH:7][C:5]2[O:6][C:2]([F:13])([F:1])[O:3][C:4]=2[CH:10]=1

Participants

6

Reactant 3

HCID 962WaterHCID 24386Thionyl Chloride2×HCID 12814281(2,2-Difluoro-1,3-dioxaindan-5-yl)methanol

Product 1

HCID 219928095-(Chloromethyl)-2,2-difluorobenzo[d][1,3]dioxole

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
20 °C

Procedure

(2,2-difluoro-1,3-benzodioxol-5-yl)-methanol (1.0 eq) is dissolved in MTBE (5 vol). A catalytic amount of DMAP (1 mol %) is added and SOCl2 (1.2 eq) is added via addition funnel. The SOCl2 is added at a rate to maintain the temperature in the reactor at 15-25° C. The temperature is increased to 30° C. for 1 hour then cooled to 20° C. then water (4 vol) is added via addition funnel maintaining the temperature at less than 30° C. After stirring for an additional 30 minutes, the layers are allowed to separate. The organic layer is stirred and 10% (w/v) aq. NaOH (4.4 vol) is added. After stirring for 15 to 20 minutes, the layers are allowed to separate. The organic phase is then dried (Na2SO4), filtered, and concentrated to afford crude 5-chloromethyl-2,2-difluoro-1,3-benzodioxole that is used directly in the next step.

Workup

  1. temperatureThe temperature is increased to 30° C. for 1 hour
  2. temperaturethen cooled to 20° C.
  3. temperaturemaintaining the temperature at less than 30° C
  4. customto separate
  5. stirringThe organic layer is stirred
  6. addition10% (w/v) aq. NaOH (4.4 vol) is added
  7. stirringAfter stirring for 15 to 20 minutes
  8. customto separate
  9. dry with materialThe organic phase is then dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-04960886e25f455cb5d15f04ee5f72bb
Source dataset
uspto-grants-2016_02
Patent number
US09254291B2

Reaction notes

Loading…