4-Toluenesulfonyl chloride → (R)-(2,3-Dihydrobenzo[b][1,4]dioxin-2-yl)methyl 4-methylbenzenesulfonate

HRID 963991Notes

Reaction equation

HRID 963991 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[O:12]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[O:15][CH2:14][C@@H:13]1[CH2:22][OH:23]>N1C=CC=CC=1>[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O:23][CH2:22][C@@H:13]2[O:12][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[O:15][CH2:14]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 676612(S)-(2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanol

Product 1

HCID 7101148(R)-(2,3-Dihydrobenzo[b][1,4]dioxin-2-yl)methyl 4-methylbenzenesulfonateYield 18.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Toluene-4-sulphonyl chloride (4.2 g) was added at -10° C. under nitrogen to a stirred solution of (S)-1,4-benzodioxan-2-ylmethanol (3.3 g) in pyridine (50 ml) The mixture was allowed to warm to ambient temperature and was stirred for a further 60 hours, then poured onto ice-water (200 ml). The product was extracted into ethyl acetate (3×200 ml) then the combined extracts were washed with dilute hydrochloric acid (100 ml), and water (100 ml), dried over magnesium sulphate, and the solvent removed in vacuo. The resulting orange oil (5.84 g), which solidified slowly on standing, was purified by crystallisation from an ether and petroleum ether (b.p. 40°-60° C.) mixture to yield two batches of a white crystalline solid (2.4 and 1.2 g). The 2.4 g batch was recrystallised 3 times from ethanol, the solid obtained becoming each time less rich in the desired (R)-isomer of the product and was therefore discarded. The mother liquors from these 3 recrystallisations now contained predominantly the desired (R)-isomer of the product so they were combined, the solvent removed in vacuo and the residue recrystallised from ethanol to yield white crystals of (R)-1,4-benzodioxan-2-ylmethyl toluene-4-sulphonate (1.2 g); m.p. 105°-107° C.

Workup

  1. additionpoured onto ice-water (200 ml)
  2. extractionThe product was extracted into ethyl acetate (3×200 ml)
  3. washthe combined extracts were washed with dilute hydrochloric acid (100 ml), and water (100 ml)
  4. dry with materialdried over magnesium sulphate
  5. customthe solvent removed in vacuo
  6. customwas purified by crystallisation from an ether and petroleum ether (b.p. 40°-60° C.) mixture
  7. customto yield two batches of a white crystalline solid (2.4 and 1.2 g)
  8. customThe 2.4 g batch was recrystallised 3 times from ethanol
  9. customthe solid obtained
  10. customThe mother liquors from these 3 recrystallisations
  11. customthe solvent removed in vacuo
  12. customthe residue recrystallised from ethanol

Sources & evidence

ORD record
ord-89ef7ba42c5c495388c5c16a47d90e1a
Source dataset
uspto-grants-1998_06
Patent number
US05767116

Reaction notes

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