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

HRID 1020448Notes

Reaction equation

HRID 1020448 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-9b9b882fa88846fa8e240c71c8101e29
Source dataset
uspto-grants-2014_05
Patent number
US08716338B2

Reaction notes

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