Hydrochloric Acid → HCID 178444524, compound

HRID 1765006Notes

Reaction equation

HRID 1765006 reaction equation
[CH2:1]([C:5]1(O)[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)[CH2:2][CH2:3][CH3:4].Br[CH2:19][C@H:20]1[CH2:25][CH2:24][C@H:23]([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:22][CH2:21]1.C(=O)([O-])[O-:32].[K+].[K+].Cl>CN(C=O)C>[CH2:1]([CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([F:16])[C:9]([F:15])=[C:10]([O:32][CH2:19][C@H:20]3[CH2:25][CH2:24][C@H:23]([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:22][CH2:21]3)[CH:11]=2)[O:6]1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 23115726HCID 23115726, compoundHCID 178444389HCID 178444389, compound

Product 1

HCID 178444524HCID 178444524, compoundYield 25.5%

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, 25.1 g bromo-trans-4-pentylcyclohexylmethane and 11.7 g of anhydrous potassium carbonate were added, and heated to reflux for 1 hour. After the reaction solution was poured into 10% hydrochloric acid, and stirred for a while, the solution was extracted with toluene. An organic layer was washed using 10% hydrochloric acid twice, water, a 5% sodium hydroxide aqueous solution twice, water, a saturated sodium hydrogen carbonate aqueous solution twive, 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 oily material was purified by carrying out column chromatography (silica gel, hexane), recrystallization (acetone/methanol), distillation under a reduced pressure (227° C./0.6 mmHg), column chromatography (silica gel, hexane/toluene), recrystallization (acetone/methanol), and recrystallization (acetone/methanol), to obtain 8.8 g of 2-butyl-7,8-difluoro-6-(trans-4-pentylcyclohexylmethoxy)chroman (Ie) as colorless crystals.

Workup

  1. temperatureheated
  2. temperatureto reflux for 1 hour
  3. extractionthe solution was extracted with toluene
  4. washAn organic layer was washed
  5. dry with materialwater, a 5% sodium hydroxide aqueous solution twice, water, a saturated sodium hydrogen carbonate aqueous solution twive, and a saturated saline solution in that order, and dried
  6. customThe solvent was evaporated under a reduced pressure
  7. customthe obtained brown oily material was purified
  8. customcolumn chromatography (silica gel, hexane), recrystallization (acetone/methanol), distillation
  9. customunder a reduced pressure (227° C./0.6 mmHg), column chromatography (silica gel, hexane/toluene), recrystallization (acetone/methanol), and recrystallization (acetone/methanol)

Sources & evidence

ORD record
ord-eb7a6bd0572d449f9a66bb0e4c89801e
Source dataset
uspto-grants-2007_06
Patent number
US07226644B2

Reaction notes

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