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

HRID 453825Notes

Reaction equation

HRID 453825 reaction equation
ClC1C=C(C=CC=1)C(OO)=[O:6].F[C:13]1[CH:14]=[CH:15][C:16]([O:22][CH2:23][C@H:24]2[CH2:26][O:25]2)=[C:17](C(=O)C)[CH:18]=1.[OH-].[Na+].[C:29]1([CH3:39])[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1.Cl>ClCCl.N1C=CC=CC=1>[O:6]1[C:17]2[CH:18]=[CH:13][CH:14]=[CH:15][C:16]=2[O:22][CH2:23][C@@H:24]1[CH2:26][O:25][S:35]([C:32]1[CH:33]=[CH:34][C:29]([CH3:39])=[CH:30][CH:31]=1)(=[O:37])=[O:36]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 14798Sodium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 866447241-[5-fluoro-2-((R)-1-oxiranylmethoxy)-phenyl]-ethanone

Product 1

HCID 7101148(R)-(2,3-Dihydrobenzo[b][1,4]dioxin-2-yl)methyl 4-methylbenzenesulfonateYield 66.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

3-Chloroperoxybenzoic acid (4.19 g, 17.00 mmol) was added in small portions to 1-[5-fluoro-2-((R)-1-oxiranylmethoxy)-phenyl]-ethanone (2.55 g, 12.13 mmol) in dichloromethane (13 ml) and the reaction mixture was refluxed for 24 hours. The cooled reaction mixture was washed twice with 10% NaHCO3 solution, once with aq NaOH solution and evaporated to dryness. 2M NaOH (10.9 ml, 21.84 mmol) was added to the evaporation residue and the mixture was heated to reflux for 1 hour. The cooled reaction mixture was extracted with dichloromethane and dichloromethane layer was evaporated to dryness. p-Toluenesulfonyl chloride (2.78 g, 14.56 mmol) was added in small portions to the evaporation residue in pyridine (7.5 ml) and the reaction mixture was stirred at RT. After 4 hours 1M HCl (7.5 ml) was added and the mixture was stirred for 1 hour at RT. The reaction mixture was extracted twice with ethyl acetate and the combined ethyl acetate layers were evaporated to dryness. The crude product was crystallized from 2-propanol to yield 2.58 g (63%) of the pure title compound.

Workup

  1. temperaturethe reaction mixture was refluxed for 24 hours
  2. customThe cooled reaction mixture
  3. washwas washed twice with 10% NaHCO3 solution, once with aq NaOH solution
  4. customevaporated to dryness
  5. temperaturethe mixture was heated
  6. temperatureto reflux for 1 hour
  7. customThe cooled reaction mixture
  8. extractionwas extracted with dichloromethane and dichloromethane layer
  9. customwas evaporated to dryness
  10. stirringthe mixture was stirred for 1 hour at RT
  11. extractionThe reaction mixture was extracted twice with ethyl acetate
  12. customthe combined ethyl acetate layers were evaporated to dryness
  13. customThe crude product was crystallized from 2-propanol

Sources & evidence

ORD record
ord-adae472db4d44f888f87d2558f9d4c29
Source dataset
uspto-grants-2013_07
Patent number
US08492549B2

Reaction notes

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