Hydrochloric Acid → HCID 178444290, compound

HRID 1780568Notes

Reaction equation

HRID 1780568 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]2[CH:25]=[CH:24][C:23]([C@H:26]3[CH2:31][CH2:30][C@H:29]([CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[N:15]=1.B(OC(C)C)(OC(C)C)[O:38]C(C)C.Cl.[Cl-].[Na+]>O1CCCC1.CCCCCC.CCOCC>[F:13][C:14]1[C:19]([OH:38])=[CH:18][CH:17]=[C:16]([C:20]2[CH:21]=[CH:22][C:23]([C@H:26]3[CH2:31][CH2:30][C@H:29]([CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH2:28][CH2:27]3)=[CH:24][CH:25]=2)[N:15]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 7912DiisopropylamineHCID 21531Triisopropyl borateHCID 178418339ButyllithiumHCID 178444267HCID 178444267, compound

Product 1

HCID 178444290HCID 178444290, compoundYield 31.3%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

0.49 ml (3.50 mmol) of diisopropylamine in 10 ml of tetrahydrofuran are stirred with 2.20 ml (3.50 mmol) of a 1.6-molar n-butyllithium solution in hexane at 0° C. for one hour. After cooling to -78° C., 0.94 g (2.90 mmol) of 2-fluoro-6-[4-(trans-4-pentylcyclohexyl)phenyl]pyridine in 120 ml of tetrahydrofuran is added dropwise, and the mixture is stirred at -78° C. for 4 hours. 1.31 g (6.96 mmol) of triisopropyl borate are then added dropwise at -78° C., and the reaction mixture is stirred overnight, during which it warms to room temperature. Addition of 4.40 ml of 10% hydrochloric acid and one hour of stirring at room temperature is followed by addition of sodium chloride solution, extraction with ether, washing of the ether phase with sodium chloride solution, drying over sodium sulfate, filtration and concentration. The residue is taken up in 50 ml of tetrahydrofuran, and the resulting mixture is refluxed together with 8.80 ml of a 17.5% hydrogen peroxide solution for 4 hours. After addition of sodium chloride solution, extraction with ether, washing of the organic phase with sodium sulfite solution and sodium chloride solution, drying over sodium sulfate, filtration, evaporation to dryness and purification of the residue by chromatography (silica gel, 9:1 hexane/ethyl acetate), 0.31 g of 2-fluoro-3-hydroxy-6-[4-(trans-4-pentylcyclohexyl)phenyl]pyridine is obtained. ##STR51##

Workup

  1. stirringthe reaction mixture is stirred overnight, during which it
  2. customwarms to room temperature
  3. stirringof stirring at room temperature
  4. washwashing of the ether phase with sodium chloride solution
  5. dry with materialdrying over sodium sulfate, filtration and concentration
  6. temperaturethe resulting mixture is refluxed together with 8.80 ml of a 17.5% hydrogen peroxide solution for 4 hours
  7. additionAfter addition of sodium chloride solution, extraction with ether
  8. washwashing of the organic phase with sodium sulfite solution and sodium chloride solution
  9. dry with materialdrying over sodium sulfate, filtration, evaporation to dryness and purification of the residue by chromatography (silica gel, 9:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-e673ec4ae3004f2ca50baaa703cbeb03
Source dataset
uspto-grants-1997_05
Patent number
US05630962

Reaction notes

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