Toluene → HCID 178438790, compound

HRID 1764997Notes

Reaction equation

HRID 1764997 reaction equation
[H-].[Na+].C1COCC1.[OH:8][CH:9]([CH2:36][CH2:37][CH3:38])[CH2:10][CH2:11][C:12]1[C:13](F)=[C:14]([F:34])[C:15]([F:33])=[C:16]([C@H:18]2[CH2:23][CH2:22][C@H:21]([C@H:24]3[CH2:29][CH2:28][C@H:27]([CH2:30][CH2:31][CH3:32])[CH2:26][CH2:25]3)[CH2:20][CH2:19]2)[CH:17]=1.C1(C)C=CC=CC=1>CN(C=O)C>[F:33][C:15]1[C:14]([F:34])=[C:13]2[C:12]([CH2:11][CH2:10][CH:9]([CH2:36][CH2:37][CH3:38])[O:8]2)=[CH:17][C:16]=1[C@H:18]1[CH2:19][CH2:20][C@H:21]([C@H:24]2[CH2:25][CH2:26][C@H:27]([CH2:30][CH2:31][CH3:32])[CH2:28][CH2:29]2)[CH2:22][CH2:23]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 178450440HCID 178450440, compound

Product 1

HCID 178438790HCID 178438790, compoundYield 29.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

Under nitrogen replacement, 1.23 g of sodium hydride (60% in oil) was suspended in 18 ml of DMF. Into this, the THF (36 mL) solution containing 9 g of 5-(3-hydroxy-1-hexyl)-2,3,4-trifluoro-1-[trans-4-(trans-4-propylcyclohexyl)cyclohexyl]benzene was added dropwise for 30 minutes, and stirred for 3 hours at 40° C. and then for 3 hours at 50° C. After toluene was added and stirred for a while, an organic layer was separated and an aqueous layer was extracted with toluene. After the extract and the organic layer were mixed together, washed using water and a saturated saline solution in that order, and dried using anhydrous sodium sulfate, the solvent was evaporated under a reduced pressure. The residue was purified by carrying out column chromatography (silica gel, hexane), recrystallization (hexane), recrystallization (hexane/ethanol) to obtain 2.5 g of 7,8-difluoro-6-[trans-4-(trans-4-propylcyclohexyl)cyclohexyl]-2-propylchroman as colorless needlelike crystals.

Workup

  1. additionwas added dropwise for 30 minutes
  2. waitfor 3 hours at 50° C
  3. stirringstirred for a while
  4. customan organic layer was separated
  5. extractionan aqueous layer was extracted with toluene
  6. extractionAfter the extract
  7. additionthe organic layer were mixed together
  8. washwashed
  9. customa saturated saline solution in that order, and dried
  10. customthe solvent was evaporated under a reduced pressure
  11. customThe residue was purified
  12. customcolumn chromatography (silica gel, hexane), recrystallization (hexane), recrystallization (hexane/ethanol)

Sources & evidence

ORD record
ord-720faf6155904fe5a70f975b99c9ac6c
Source dataset
uspto-grants-2007_06
Patent number
US07226644B2

Reaction notes

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