N,N,N',N'-Tetramethylethylenediamine → 4,5-difluoro-7-pentyl-2-(4-propylcyclohexyl)-8,9-dihydro-7H-furo[3,2-f]chromene

HRID 2244843Notes

Reaction equation

HRID 2244843 reaction equation
[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[O:9]2)=[C:4]([C:18]#[C:19][CH:20]2[CH2:25][CH2:24][CH:23]([CH2:26][CH2:27][CH3:28])[CH2:22][CH2:21]2)[C:3]=1[OH:29].CN(CCN(C)C)C.C([Zn]CC)C.[Cl-].[NH4+]>C1(C)C=CC=CC=1>[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[O:9]2)=[C:4]2[CH:18]=[C:19]([CH:20]3[CH2:21][CH2:22][CH:23]([CH2:26][CH2:27][CH3:28])[CH2:24][CH2:25]3)[O:29][C:3]=12

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 592152687,8-Difluoro-2-pentyl-5-(4-propylcyclohexylethynyl)chroman-6-olHCID 178418750HCID 178418750, compound

Product 1

HCID 592152444,5-difluoro-7-pentyl-2-(4-propylcyclohexyl)-8,9-dihydro-7H-furo[3,2-f]chromene

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

3.00 g (7.41 mmol) of 7,8-difluoro-2-pentyl-5-(4-propylcyclohexylethynyl)chroman-6-ol are initially introduced together with 0.11 ml (0.74 mmol) of TMEDA, and 4.1 ml (4.1 mmol) of diethylzinc (1 M soln. in heptane) are added to the mixture at 3° C. When the evolution of gas has subsided, 11 ml of toluene are added, and the batch is refluxed for 40 h. The solution is added to sat. ammonium chloride soln., and the mixture is extracted with toluene. The combined organic phases are washed with water 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, 1-chlorobutane:pentane=2:1). Further purification is carried out by repeated recrystallisation from ethanol at reduced temperature, giving 4,5-difluoro-7-pentyl-2-(4-propylcyclohexyl)-8,9-dihydro-7H-furo[3,2-f]chromene as a colourless solid having the phase sequence C 56° C. N 62° C. I (Δ∈=−6.8).

Workup

  1. additionare added to the mixture at 3° C
  2. temperaturethe batch is refluxed for 40 h
  3. extraction, and the mixture is extracted with toluene
  4. washThe combined organic phases are washed with water and sat. sodium chloride soln
  5. customand dried
  6. concentrationThe solution is concentrated to dryness
  7. customthe residue is purified by column chromatography (SiO2, 1-chlorobutane:pentane=2:1)
  8. customFurther purification
  9. customrecrystallisation from ethanol at reduced temperature

Sources & evidence

ORD record
ord-e7d2575ccf864a5fbe1d233b792a2aba
Source dataset
uspto-grants-2010_03
Patent number
US07678929B2

Reaction notes

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