Acetic Acid → HCID 12908985, compound

HRID 1583911Notes

Reaction equation

HRID 1583911 reaction equation
[F:1][C:2]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:13]=[C:12]2[C:8]([CH2:9][CH2:10][CH2:11]2)=[CH:7][C:6]=1[NH2:14].[C:20](OC(=O)C)(=[O:22])[CH3:21].C(O)(=[O:29])C>O.[O-2].[O-2].[O-2].[Cr+6]>[C:20]([NH:14][C:6]1[CH:7]=[C:8]2[C:12]([CH2:11][CH2:10][C:9]2=[O:29])=[CH:13][C:5]=1[O:4][C:3]1[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:2]=1[F:1])(=[O:22])[CH3:21]

Participants

6

Reactant 3

HCID 176Acetic Acid2×HCID 7918Acetic AnhydrideHCID 128870866-(2,4-Difluorophenoxy)-2,3-dihydro-1H-inden-5-amine

Product 1

HCID 12908985HCID 12908985, compound

Reagents, catalysts & solvents 2

HCID 10219390chromium (VI) trioxideCatalystHCID 962WaterSolvent

Procedure

120 g of 6-(2,4-difluorophenoxy)-5-indanylamine is kept in 1.2 l of acetic acid and 0.5 l of acetic anhydride for 30 minutes at 50° C. and then, at this temperature, a solution of chromium trioxide (110 g) in 50 ml of water and 300 ml of acetic acid is added dropwise thereto. After 30 minutes at 50° C., the mixture is concentrated, water is added, the mixture is extracted with chloroform and chromatographed with chloroform over a silica gel column, yielding 30 g of 6-acetylamino-5-(2,4-difluorophenoxy)-1indanone, mp 210° C. This quantity is dissolved in 500 ml of tetrahydrofuran, and the solution is combined at 40° C. with a phenylmagnesium bromide solution in ether (prepared from 24 g of magnesium, 108 ml of bromobenzene, and 500 ml of ether). After 16 hours at 20° C., the mixture is decomposed with ammonium chloride solution. The organic phase is stirred for 5 minutes with 8 g of p-toluenesulfonic acid. After filtration, the mixture is concentrated, the residue is extracted by stirring with petroleum ether and recrystallized from ethanol, thus obtaining 22 g of N-[6-(2,4-difluorophenoxy)-3-phenyl-5-indenyl]acetamide. This product is dissolved in 60 ml of dioxane and 240 ml of ethanol and hydrogenated over 1.2 g of palladium-charcoal (10%). Concentration and crystallization from petroleum ether yield 16.5 g of N-[6-(2,4-difluorophenoxy)-3-phenyl-5-indanyl]acetamide, mp 117° C. This product is stirred in 200 ml of acetone with a solution of 8 g of chromium trioxide, 20 ml of sulfuric acid, and 40 ml of acetic acid for 16 hours at 20° C. After adding sodium bisulfite, the mixture is concentrated, taken up in chloroform, the chloroform solution is washed with sodium hydroxide solution and concentrated. Chromatography over silica gel with toluene-ethyl acetate yields 6 g of 5-acetylamino-6-(2,4-difluorophenoxy)-3-phenyl-1-indanone, mp 163° C. This quantity is refluxed in 50 ml of ethanol and 10 ml of hydrochloric acid (10-normal) for 2 hours. After concentration, the mixture is made weakly alkaline with ammonia, vacuum-filtered, dried, taken up in 60 ml of pyridine, and combined with 2.3 g of methanesulfonyl chloride. The mixture is concentrated after having been left for 25 hours at 20° C., combined with water, vacuum-filtered, dissolved in 1N sodium hydroxide solution, and acidified with 10N hydrochloric acid. Vacuum-filtering yields 3.1 g of 6-(2,4-difluorophenoxy)-5-methylsulfonylamino-3-phenyl-1-indanone, mp 101° C.

Workup

  1. concentrationthe mixture is concentrated
  2. additionwater is added
  3. extractionthe mixture is extracted with chloroform
  4. customchromatographed with chloroform over a silica gel column

Sources & evidence

ORD record
ord-e55c6971c7c54e13a9fff6b5d513c7e9
Source dataset
uspto-grants-1985_11
Patent number
US04555406

Reaction notes

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