Methyl iodide → 4,6-Difluoro-2-methyl-2,3-dihydro-1H-inden-1-one
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].[CH:13]([N-]C(C)C)(C)C.[Li+].IC.C([O-])(O)=O.[Na+]>O1CCCC1>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH3:13])[C:6]2=[O:12]Participants
6
Conditions
- Temperature
- -78 °C
Procedure
According to Scheme 3, step 1: to a solution of 4,6-difluoro-indan-1-one (5.0 g, 29.8 mmol) in dry tetrahydrofuran (100 ml) at −78° C. a 2M solution of lithiumdiisopropylamide (16.4 ml, 32.7 mmol) in tetrahydrofuran was added dropwise and the mixture was stirred for 1 h at −78° C. Then iodomethane (4.64 g, 32.7 mmol) was added and the mixture was slowly warmed to 25° C. After addition of aqueous saturated NaHCO3 the mixture was extracted 3 times with ethyl acetate. The combined organic layers were dried over Na2SO4 and filtered, solvents were evaporated in vacuo. The crude product was purified by silica gel chromatography (eluting with 0% to 100% ethyl acetate in heptane to give 1.15 g of 4,6-Difluoro-2-methyl-indan-1-one (7a).
Workup
- temperaturethe mixture was slowly warmed to 25° C
- extractionwas extracted 3 times with ethyl acetate
- dry with materialThe combined organic layers were dried over Na2SO4
- filtrationfiltered
- customsolvents were evaporated in vacuo
- customThe crude product was purified by silica gel chromatography (
- washeluting with 0% to 100% ethyl acetate in heptane
Sources & evidence
- ORD record
- ord-d63504172c914fc7abc694400a02d4d2
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09034897B2
Reaction notes
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