Hydrochloric Acid → HCID 18180304, compound

HRID 1359065Notes

Reaction equation

HRID 1359065 reaction equation
Cl.[CH3:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([O:12][CH2:13][C@H:14]2[O:19][C:18]3[CH:20]=[C:21]([NH2:26])[C:22]([O:24][CH3:25])=[CH:23][C:17]=3[O:16][CH2:15]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.Cl.Cl[C:29]1[C:30](=O)C2C(C(=O)[C:38]=1Cl)=CC=CC=2.C(C=C)=O.[OH-].[Na+]>C(O)C>[CH3:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([O:12][CH2:13][CH:14]2[O:19][C:18]3=[C:20]4[C:21](=[C:22]([O:24][CH3:25])[CH:23]=[C:17]3[O:16][CH2:15]2)[N:26]=[CH:30][CH:29]=[CH:38]4)(=[O:10])=[O:11])=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7847AcroleinHCID 8342DichloneHCID 14798Sodium HydroxideHCID 86586356HCID 86586356, compound

Product 1

HCID 18180304HCID 18180304, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To 1.50 g (3.73 mmole) of [(2S)-7-amino-6-methoxy-2,3-dihydro-1,4-benzodioxin-2y]methyl 4-methylbenzenesulfonate hydrochloride was added 100 mL of concentrated hydrochloric acid. Then 0.85 g (3.74 mmole) of 2,3-dichloro-1,4-naphthoquinone was added with sufficient ethanol to wash down the solid. The heterogeneous mixture was heated to reflux and a solution of 0.31 g (5.53 mmole) of acrolein in 10 mL of ethanol was added dropwise. Reflux was continued for an additional 1 hour. The mixture was then allowed to come to room temperature and added to ice water. The solution was made basic with 1 N NaOH and extracted with methylene chloride. The extract was dried over magnesium sulfate, filtered and concentrated to a crude brown oil in vacuum. This was column chromatographed on silica gel with a gradient elution commencing with methylene chloride and ending with 3% methanol in methylene chloride and the product-containing fractions concentrated in vacuum to give 0.75 g of the (R)-enantiomer of the title compound as a yellow oil. 1H-NMR (CDCl3): doublet 8.8 δ(1 H); doublet 8.2 δ(1 H); doublet 7.8 δ(2 H); multiplet 7.4 δ(1 H); multiplet 7.2-7.25 δ(3 H); multiplet 4.45 δ(1 H); multiplet 4.1-4.4 δ(4 H); singlet 3.0 δ(3 H); singlet 2.4 δ(1 H).

Workup

  1. washto wash down the solid
  2. temperatureThe heterogeneous mixture was heated
  3. temperatureto reflux
  4. temperatureReflux
  5. customto come to room temperature
  6. extractionextracted with methylene chloride
  7. dry with materialThe extract was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a crude brown oil in vacuum
  10. customThis was column chromatographed on silica gel with a gradient elution commencing with methylene chloride
  11. concentrationthe product-containing fractions concentrated in vacuum

Sources & evidence

ORD record
ord-dc5c3638aab04265ac7da24c9e4869a2
Source dataset
uspto-grants-2003_07
Patent number
US06599915B2

Reaction notes

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