Formaldehyde → 4-fluoro-2-methylene-2,3-dihydro-1H-inden-1-one

HRID 473002Notes

Reaction equation

HRID 473002 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:11].C=O.[C:14]1(B(O)O)C=CC=CC=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C:5](=[CH2:14])[C:6]2=[O:11]

Participants

7

Reactant 5

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 121749864-Fluoro-1-indanone

Product 1

HCID 581981174-fluoro-2-methylene-2,3-dihydro-1H-inden-1-oneYield 72%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a 1000 mL round bottle flask were charged 4-fluoro-2,3-dihydro-1H-inden-1-one (249a) (5.04 g, 33.6 mmol), paraformaldehyde (10.08 g, 336 mmol), phenylboronic acid (4.92 g, 40.3 mmol) followed by toluene (235 mL), to the suspension was added TFA 2.6 mL, 33.6 mmol), and the resulting suspension was refluxed for 4 hrs, which resulted a clear yellowish solution. The solution was cooled to room temperature, and the pH was adjusted to 7-8 by adding saturated NaHCO3. After extracting with ethyl acetate, the organic layers were combined, and evaporated. The residue was purified by flash chromatography (0 to 30% EtOAc/Hexane) to give 4-fluoro-2-methylene-2,3-dihydro-1H-inden-1-one (249b) (3.91 g, 72%). LC-MS tR=1.49 min in 3 min chromatography, MS (ESI) m/z 163 [M+H]+

Workup

  1. temperaturewas refluxed for 4 hrs
  2. customwhich resulted a clear yellowish solution
  3. extractionAfter extracting with ethyl acetate
  4. customevaporated
  5. customThe residue was purified by flash chromatography (0 to 30% EtOAc/Hexane)

Sources & evidence

ORD record
ord-81204a30f56c4039b4c1fd6abc0a74e0
Source dataset
uspto-grants-2014_01
Patent number
US08633212B2

Reaction notes

Loading…