Hydrochloric Acid → HCID 18180309, compound

HRID 1359061Notes

Reaction equation

HRID 1359061 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]([NH2:25])[C:22]([F:24])=[CH:23][C:17]=3[O:16][CH2:15]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.Cl.[C:27]1(Cl)[C:33](=O)C(Cl)=C(Cl)C(=O)[C:28]=1Cl.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]([F:24])[CH:23]=[C:17]3[O:16][CH2:15]2)[N:25]=[CH:33][CH:27]=[CH:28]4)(=[O:11])=[O:10])=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7847AcroleinHCID 8371ChloranilHCID 14798Sodium HydroxideHCID 86587359HCID 86587359, compound

Product 1

HCID 18180309HCID 18180309, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To 1.06 g (2.72 mmole) of [(2S)-7-amino-6-fluoro-2,3-dihydro-1,4-benzodioxin-2y]methyl 4-methylbenzenesulfonate hydrochloride was added 100 mL of concentrated hydrochloric acid. Then 0.66 g (2.68 mmole) of p-chloranil was added with sufficient ethanol to wash down the solid. The heterogeneous mixture was heated to reflux and a solution of 0.25 g (4.45 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 1:1 hexane/ethyl acetate and the product-containing fractions concentrated in vacuum to give 0.60 g of the (R)-enantiomer of the title compound as a yellow oil. 1H-NMR (CDCl3): doublet 8.6 δ(1 H); doublet 8.2 δ(1 H); doublet 7.75 δ(2 H); multiplet 7.4 δ(1 H); doublet 7.25 δ(2 H); doublet 7.0 δ(1 H); multiplet 4.58 δ(1 H); multiplet 4.2-4.4 δ(3 H); multiplet 4.2 δ(1 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 1:1 hexane/ethyl acetate
  11. concentrationthe product-containing fractions concentrated in vacuum

Sources & evidence

ORD record
ord-e2a25b8ccedf4362a50496f9822ccd9d
Source dataset
uspto-grants-2003_07
Patent number
US06599915B2

Reaction notes

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