Hydrochloric Acid → 5,6-Difluoro-8-(4-propylcyclohexyl)-1,2,3,8-tetrahydropyrano[3,2-f]chromene

HRID 1873306Notes

Reaction equation

HRID 1873306 reaction equation
[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][O:9]2)=[CH:4][C:3]=1[O:13][CH:14]([CH:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH2:24][CH3:25])[CH2:19][CH2:18]1)[C:15]#[CH:16].[F-].[K+].O.Cl>C(N(CC)C1C=CC=CC=1)C>[F:12][C:11]1[C:2]([F:1])=[C:3]2[C:4]([CH:16]=[CH:15][CH:14]([CH:17]3[CH2:18][CH2:19][CH:20]([CH2:23][CH2:24][CH3:25])[CH2:21][CH2:22]3)[O:13]2)=[C:5]2[CH2:6][CH2:7][CH2:8][O:9][C:10]=12

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 522689Potassium FluorideHCID 581519137,8-Difluoro-6-[1-(4-propylcyclohexyl)prop-2-ynyloxy]chroman

Product 1

HCID 581519065,6-Difluoro-8-(4-propylcyclohexyl)-1,2,3,8-tetrahydropyrano[3,2-f]chromene

Reagents, catalysts & solvents 1

HCID 7061N,N-DiethylanilineSolvent

Procedure

6.0 g (17.2 mmol) of 7,8-difluoro-6-[1-(4-propylcyclohexyl)prop-2-ynyloxy]-chroman are heated at 200° C. for 6 h together with 2.0 g (34.4 mmol) of potassium fluoride in 55 ml of N,N-diethylaniline. After cooling, water is added, and the mixture is acidified using 25% hydrochloric acid. The batch is extracted with MTBE, and the organic phase is washed with saturated sodium chloride solution. The solution is dried using sodium sulfate and evaporated to dryness. The crude product is purified by column chromatography (SiO2, 1-chlorobutane), giving 5,6-difluoro-8-(4-propylcyclohexyl)-1,2,3,8-tetrahydropyrano[3,2-f]chromene as a pale-brown oil.

Workup

  1. temperatureAfter cooling
  2. extractionThe batch is extracted with MTBE
  3. washthe organic phase is washed with saturated sodium chloride solution
  4. customThe solution is dried
  5. customevaporated to dryness
  6. customThe crude product is purified by column chromatography (SiO2, 1-chlorobutane)

Sources & evidence

ORD record
ord-2ac63e8aef864433a077c3bfb7db7e0d
Source dataset
uspto-grants-2012_11
Patent number
US08303844B2

Reaction notes

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