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

HRID 870791Notes

Reaction equation

HRID 870791 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) was dissolved in MTBE (5 vol). A catalytic amount of 4-(N,N-dimethyl)aminopyridine (DMAP) (1 mol %) was added and SOCl2 (1.2 eq) was added via addition funnel. The SOCl2 was added at a rate to maintain the temperature in the reactor at 15 to 25° C. The temperature was increased to 30° C. for 1 hour, and then was cooled to 20° C. Water (4 vol) was added via addition funnel while maintaining the temperature at less than 30° C. After stirring for an additional 30 minutes, the layers were allowed to separate. The organic layer was stirred, and 10% (w/v) aq NaOH (4.4 vol) was added. After stirring for 15 to 20 minutes, the layers were allowed to separate. The organic phase was then dried (Na2SO4), filtered, and concentrated to afford crude 5-chloromethyl-2,2-difluoro-1,3-benzodioxole that was used directly in the next step.

Workup

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

Sources & evidence

ORD record
ord-67879fba7d594d34a5e75bb654b59bf3
Source dataset
uspto-grants-2015_03
Patent number
US08969574B2

Reaction notes

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