Iodine → HCID 123511408, compound

HRID 1508473Notes

Reaction equation

HRID 1508473 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH:8]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:7][CH2:6]2.[I:18]I>C(O)C.C(OCC)(=O)C.S([O-])([O-])(=O)=O.[Ag+2]>[I:18][C:11]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH:8]2[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][C:3]=1[O:2][CH3:1]

Participants

6

Reactant 2

HCID 807IodineHCID 10263432Ethyl 2-(5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 123511408HCID 123511408, compound

Reagents, catalysts & solvents 3

HCID 178418844HCID 178418844, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl (5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate (472 mg, 2.015 mmol) was dissolved in ethanol (20 mL). Iodine (511 mg, 2.015 mmol) and silver sulfate (628 mg, 2.015 mmol) were added and the reaction was stirred vigorously at room temperature, protected from light, for 1 hour. The reaction was diluted with ethyl acetate (75 mL) and filtered to remove solids. The filtrate was washed with sodium bisulfite (2×50 mL), water (70 mL), and brine (70 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 0 to 50% ethyl acetate/hexanes. Further purification by SFC on a chiral AD column with 15% IPA/heptanes removed a minor regioisomer and separated the two enantiomers of ethyl (6-iodo-5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate. 1H NMR (CDCl3, 500 MHz) δ 7.55 (s, 1H), 6.72 (s, 1H), 4.17 (m, 2H), 3.85 (s, 3H), 3.53 (m, 1H), 2.95-2.65 (m, 3H), 2.60-2.42 (m, 2H), 1.78 (m, 1H), 1.28 (t, J=7.1 Hz, 3H).

Workup

  1. customfor 1 hour
  2. filtrationfiltered
  3. customto remove solids
  4. washThe filtrate was washed with sodium bisulfite (2×50 mL), water (70 mL), and brine (70 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography on silica gel with 0 to 50% ethyl acetate/hexanes
  9. customFurther purification by SFC on a chiral AD column with 15% IPA/heptanes
  10. customremoved a minor regioisomer
  11. customseparated the two enantiomers of ethyl (6-iodo-5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate

Sources & evidence

ORD record
ord-e1c922229d0940068b3508d1e2fd2b07
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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