Iodine → Ethyl 2-(4,6-difluoro-1-hydroxy-1-indanyl)acetate

HRID 362818

Reaction equation

HRID 362818 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:12].Br[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].II>C(OCC)C.C1(C)C=CC=CC=1.[Zn]>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[OH:12]

Participants

6

Reactant 3

HCID 807Iodine2×HCID 7748Ethyl bromoacetateHCID 109539204,6-difluoro-2,3-dihydro-1H-inden-1-one

Product 1

HCID 11780116Ethyl 2-(4,6-difluoro-1-hydroxy-1-indanyl)acetateYield 110.7%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 22238780Ether tolueneSolvent

Procedure

A mixture of 4,6-difluoro-1-indanone (12.6 g, 0.08 mol), ethyl bromoacetate (19.0 g, 0.11 mol, Aldrich), activated zinc powder (7.5 g, 0.11 mol, Aldrich; Org. Syn., Coll. Vol. 6, 290, 1988) and a few crystals of iodine in diethyl ether:toluene (1:1, 300 mL) was heated at 30°-35° C. under a nitrogen atmosphere for 24 h. A few more crystals of iodine were added, the temperature was adjusted to 40°-45° C., and the mixture was kept at that temperature for an additional 24 h. The reaction mixture was filtered and concentrated in vacuo. The residue was treated with a mixture of diethyl ether (450 mL), concentrated ammonium hydroxide (135 mL) and water (135 mL). The aqueous phase was separated and extracted with diethyl ether. The combined organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo to give 22.7 g of crude Ethyl 2-(4,6-difluoro-1- hydroxy-1-indanyl)acetate which was Chromatographed on silica gel with dichloromethane:hexanes (9:1) as eluent gave 12.7 g (66%) of a yellow oil; NMR (CDCl3): d 6.67-6.88 (m, 2H), 4.22 (q, 2H), 3.02 (m, 1H), 2.75 (2 m's, 3H), 2.31 (m, 2H), 1.28 (t, 3H).

Workup

  1. customwas adjusted to 40°-45° C.
  2. filtrationThe reaction mixture was filtered
  3. concentrationconcentrated in vacuo
  4. additionThe residue was treated with a mixture of diethyl ether (450 mL), concentrated ammonium hydroxide (135 mL) and water (135 mL)
  5. customThe aqueous phase was separated
  6. extractionextracted with diethyl ether
  7. washThe combined organic phase was washed with saturated aqueous sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-80db2b219d3b40fb98b50d3989a79eba
Source dataset
uspto-grants-1999_02
Patent number
US05872118

Linked notes

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