3-Bromopyridine → (4-Methoxyphenyl)(pyridine-3-yl)methanol

HRID 647091Notes

Reaction equation

HRID 647091 reaction equation
C([Li])CCC.BrN1C=CC=NC1.Br[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=[O:27])=[CH:24][CH:23]=1>O1CCCC1.C(OCC)C>[N:16]1[CH:17]=[CH:18][CH:19]=[C:14]([CH:26]([C:25]2[CH:28]=[CH:29][C:22]([O:21][CH3:20])=[CH:23][CH:24]=2)[OH:27])[CH:15]=1

Participants

7

Reactant 4

HCID 122863-BromopyridineHCID 312444-Methoxybenzaldehyde2×HCID 204856353-BromopyrimidineHCID 178418339Butyllithium

Product 1

HCID 10036218(4-Methoxyphenyl)(pyridine-3-yl)methanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-120 °C

Procedure

To a 500-ml 3-neck round bottom flask equipped with an addition funnel, septum, thermometer and an argon inlet is added 150 ml of anhydrous diethylether and 94 ml of 1.6 molar butyllithium solution (in hexane). The system is cooled to -120° C. and 23.8 gm of 3-bromopyrimidine in 75 ml of anhydrous tetrahydrofuran is added over 2 hours. After addition of the 3-bromopyridine, the system is stirred for an additional 45 minutes at this time, 18.3 ml of 4-methoxybenzaldehyde in 75 ml of tetrahydrofuran is added to the system while maintaining a temperature of -120° C. The system is kept at -120° C. for an additional 5 hours after addition of the 4-methoxy-benzaldehyde and afterwards the system is allowed to come to room temperature. After 10 hours at room temperature, the system is quenched with saturated ammonium chloride (in water). The system is adjusted to pH 2 with concentrated HCl solution. The solution is extracted with ether. The aqueous solution is then made basic with a 50% NaOH solution. The product is extracted with methylene chloride which then dried over sodium sulfate. The methylene chloride is removed by stripping and the residue triturated with hexane to give the 3-pyridyl-4-methoxyphenylcarbinol, which is converted to the compounds of this invention as described in Examples 1-7.

Workup

  1. customTo a 500-ml 3-neck round bottom flask equipped with an addition funnel
  2. additionis added to the system
  3. temperaturewhile maintaining a temperature of -120° C
  4. customto come to room temperature
  5. waitAfter 10 hours at room temperature
  6. customthe system is quenched with saturated ammonium chloride (in water)
  7. extractionThe solution is extracted with ether
  8. extractionThe product is extracted with methylene chloride which
  9. dry with materialthen dried over sodium sulfate
  10. customThe methylene chloride is removed
  11. customthe residue triturated with hexane

Sources & evidence

ORD record
ord-873a2bb5b30c44b8a1784bf742cf7108
Source dataset
uspto-grants-1983_10
Patent number
US04407806

Reaction notes

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