2-Thiophenecarboxaldehyde → HCID 19080718, compound

HRID 234598Notes

Reaction equation

HRID 234598 reaction equation
C([N-]C(C)C)(C)C.[Li+].[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[CH:14]=[O:15].[Cl-:16].[NH4+:17].[CH3:18][CH2:19][CH2:20][CH2:21][CH2:22]C>COCCOC.C1CCCCC1>[Cl:16][C:20]1[CH:21]=[CH:22][N:17]=[CH:18][C:19]=1[CH:14]([C:10]1[S:9][CH:13]=[CH:12][CH:11]=1)[OH:15]

Participants

7

Reactant 4

HCID 73642-ThiophenecarboxaldehydeHCID 8058HexaneHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamide

Product 1

HCID 19080718HCID 19080718, compound

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8078CyclohexaneSolvent

Conditions

Temperature
-70 °C

Procedure

15 g of 4-chloro pyridine hydrochloride were placed into 90 ml of diethyl ether in a 500 ml beaker equipped with a magnetic stirrer. 4.0 g of sodium hydroxide in 90 ml of water were added at 0° C. and the mixture stirred for 15 minutes. The diethyl ether layer was separated, washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo. The 10.3 g of the 4-chloropyridine produced were placed into a 3-necked flask and dissolved in 100 ml of ethylene glycol dimethyl ether (DME). After cooling to -70° C., 62 ml of 1.5M solution of lithium diisopropyl amide (LDA) in cyclohexane were added over a period of 30 minutes while maintaining the temperature below -60° C. Upon completion of the addition, the reaction mixture was stirred an additional hour at -70° C. To this cooled mixture were then added 10.7 g of 2-thiophenecarboxaldehyde. The reaction mixture was stirred in a dry-ice bath for 2 hours and then left at room temperature overnight. 100 ml of saturated ammonium chloride solution were added to the reaction mixture, and the mixture was stirred for 15 minutes at room temperature. The mixture was then extracted twice with ethyl ether. The combined ether extracts were then washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the crude product as a semi-solid. Trituration with hexane then afforded crystals which were isolated through filtration. 14.5 g of 1-(4-chloropyrid-3-yl)-1-(thien-2-yl)methanol were obtained.

Workup

  1. customwere placed into a 3-necked flask
  2. temperaturewhile maintaining the temperature below -60° C
  3. additionUpon completion of the addition
  4. stirringThe reaction mixture was stirred in a dry-ice bath for 2 hours
  5. stirringthe mixture was stirred for 15 minutes at room temperature
  6. extractionThe mixture was then extracted twice with ethyl ether
  7. washThe combined ether extracts were then washed with water
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto afford the crude product as a semi-solid
  12. customwere isolated through filtration

Sources & evidence

ORD record
ord-d8b7833040824e5d92f6123efd471bed
Source dataset
uspto-grants-1997_01
Patent number
US05595958

Reaction notes

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