Hydrochloric Acid → HCID 178450083, compound

HRID 1765007Notes

Reaction equation

HRID 1765007 reaction equation
C([C:5]1([OH:17])[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([F:16])[C:9]([F:15])=[CH:10][CH:11]=2)[O:6]1)CCC.CS([O:22][CH2:23][CH:24]1[CH2:29][CH2:28][CH:27]([C@H:30]2[CH2:35][CH2:34][C@H:33]([CH2:36][CH3:37])[CH2:32][CH2:31]2)[CH2:26][CH2:25]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C>[CH2:12]([O:17][CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([F:16])[C:9]([F:15])=[C:10]([O:22][CH2:23][C@H:24]3[CH2:29][CH2:28][C@H:27]([C@H:30]4[CH2:35][CH2:34][C@H:33]([CH2:36][CH3:37])[CH2:32][CH2:31]4)[CH2:26][CH2:25]3)[CH:11]=2)[O:6]1)[CH2:7][CH2:8][CH3:9]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 23115726HCID 23115726, compoundHCID 178455719HCID 178455719, compound

Product 1

HCID 178450083HCID 178450083, compoundYield 74.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 20.5 g of 2-butyl-7,8-difluorochroman-2-ol which was dissolved in 70 mL of DMF, 25 g of 4-(trans-4-ethylcyclohexyl)cyclohexylmethyl methanesulfonate and 11.4 g of anhydrous potassium carbonate were added, and heated to reflux for 3 hours. The reaction solution was poured into 10% hydrochloric acid, stirred for a while, and extracted with toluene. An organic layer was washed using 10% hydrochloric acid twive, water, a 5% sodium hydroxide aqueous solution twice, water, a saturated sodium hydrogen carbonate aqueous solution twice, and a saturated saline solution in that order, and dried using anhydrous magnesium sulfate. The solvent was evaporated under a reduced pressure, and the obtained brown solid material was purified by carrying out column chromatography (silica gel, hexane/toluene), recrystallization (hexane), recrystallization (acetone), and recrystallization (acetone), to obtain 14.7 g of 2-butoxy-7,8-difluoro-6-(trans-4-(trans-4-ethylcyclohexyl)cyclohexylmethoxy) chroman (If) as a colorless crystal.

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 hours
  3. extractionextracted with toluene
  4. washAn organic layer was washed
  5. dry with materiala 5% sodium hydroxide aqueous solution twice, water, a saturated sodium hydrogen carbonate aqueous solution twice, and a saturated saline solution in that order, and dried
  6. customThe solvent was evaporated under a reduced pressure
  7. customthe obtained brown solid material was purified
  8. customcolumn chromatography (silica gel, hexane/toluene), recrystallization (hexane), recrystallization (acetone), and recrystallization (acetone)

Sources & evidence

ORD record
ord-8af405a431774b42b4cfb47f0153bd5c
Source dataset
uspto-grants-2007_06
Patent number
US07226644B2

Reaction notes

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