Ammonia → 2-[4-(4-Ethylcyclohexyl)-2,3-difluorophenyl]-5-methylselenophene

HRID 1873410Notes

Reaction equation

HRID 1873410 reaction equation
[Li][CH2:2]CCC.[CH2:6]([CH:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[Se:21][CH:22]=[CH:23][CH:24]=3)=[C:16]([F:25])[C:15]=2[F:26])[CH2:10][CH2:9]1)[CH3:7].CI.[Cl-].[NH4+].N>C(OCC)C>[CH2:6]([CH:8]1[CH2:9][CH2:10][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[Se:21][C:22]([CH3:2])=[CH:23][CH:24]=3)=[C:16]([F:25])[C:15]=2[F:26])[CH2:12][CH2:13]1)[CH3:7]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 594563492-[4-(4-Ethylcyclohexyl)-2,3-difluorophenyl]selenopheneHCID 178418339Butyllithium

Product 1

HCID 594562882-[4-(4-Ethylcyclohexyl)-2,3-difluorophenyl]-5-methylselenophene

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

2.2 ml (13.0 mmol) of TMP are initially introduced at −15° C. in 15 ml of diethyl ether, and 8.2 ml (13.0 mmol, 15% soln. in hexane) of n-BuLi are metered in. After 25 min, a solution of 3.5 g (9.9 mmol) of 2-[4-(4-ethyl-cyclohexyl)-2,3-difluorophenyl]selenophene in 35 ml of diethyl ether is metered in at 0° C., and the mixture is stirred at RT for 2 h. The batch is cooled to −70° C., and 3.0 ml (48.2 mmol) of methyl iodide are added. The mixture is warmed to RT and stirred for 24 h. Sat. ammonium chloride soln. and conc. ammonia soln. are added successively, and the mixture is briefly stirred vigorously. The organic phase is separated off, and the aqueous phase is extracted with MTBE. The combined organic phases are washed with 2 N hydrochloric acid and sat. sodium chloride soln. and dried using sodium sulfate. The solution is concentrated to dryness, and the residue is purified by column chromatography (SiO2, n-heptane). The further purification is carried out by recrystallisation from ethanol. 2-[4-(4-Ethylcyclohexyl)-2,3-difluorophenyl]-5-methylselenophene is obtained as a solid having an m.p. of 63° C.

Workup

  1. customis metered in at 0° C.
  2. temperatureThe batch is cooled to −70° C.
  3. temperatureThe mixture is warmed to RT
  4. stirringstirred for 24 h
  5. additionare added successively
  6. stirringthe mixture is briefly stirred vigorously
  7. customThe organic phase is separated off
  8. extractionthe aqueous phase is extracted with MTBE
  9. washThe combined organic phases are washed with 2 N hydrochloric acid and sat. sodium chloride soln
  10. customand dried
  11. concentrationThe solution is concentrated to dryness
  12. customthe residue is purified by column chromatography (SiO2, n-heptane)
  13. customThe further purification
  14. customis carried out by recrystallisation from ethanol

Sources & evidence

ORD record
ord-2e12a41be212405cb21f8be673ee3aba
Source dataset
uspto-grants-2012_11
Patent number
US08304036B2

Reaction notes

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