Ethanethiol → 5-[(4-Chlorophenyl)methoxy]pyridine-2-carboxamide

HRID 1995829Notes

Reaction equation

HRID 1995829 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([NH2:11])=[O:10])=[N:7][CH:8]=1.[Na].C(S)C.[Cl:16][C:17]1[CH:24]=[CH:23][C:20](CCl)=[CH:19][CH:18]=1.ClC1C=CC(CCl)=CC=1.CN(C=O)C>CN(C=O)C.C(OCC)(=O)C>[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:1][O:2][C:3]2[CH:4]=[CH:5][C:6]([C:9]([NH2:11])=[O:10])=[N:7][CH:8]=2)=[CH:19][CH:18]=1

Participants

8

Reactant 5

HCID 6343EthanethiolHCID 77231-Chloro-4-(chloromethyl)benzeneHCID 5360545SodiumHCID 204860695-Methoxypyridine-2-carboxamideHCID 131713102HCID 131713102, compound

Product 1

HCID 204861105-[(4-Chlorophenyl)methoxy]pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To 5-methoxy-2-pyridylcarboxamide (2 g, 13.2 mmol) in 5 ml of DMF at RT is added the sodium salt of ethanethiol (26.3 mmol) in DMF (61.5 ml). The slurry is heated to 110° with stirring for about 15 minutes. The reaction is cooled to 50° and 40 ml of DMF is added. After 0.5 hour, the reaction is cooled to 10° and 4-chlorobenzyl chloride (2.47 g, 15.4 mmol) is added. The reaction is allowed to warm to RT and is stirred for 3 days. About 0.5 ml of 4-chlorobenzyl chloride/DMF (0.21 g/l ml) is added. After 2 hours at RT, the reaction is poured into ice water and ethyl acetate. The ethyl acetate is extracted off, and the water layer is extracted with ethyl acetate (4×). The combined organic layers are washed with water and with brine, dried, filtered and rotoevaporated. The residue is washed with 20% ether/hexane (4× ). The liquid is pipetted off and the residue is rotoevaporated to give 5-(4-chlorobenzyloxy)-2-pyridylcarboxamide.

Workup

  1. temperatureThe slurry is heated to 110°
  2. temperatureThe reaction is cooled to 50°
  3. waitAfter 0.5 hour
  4. temperaturethe reaction is cooled to 10°
  5. stirringis stirred for 3 days
  6. waitAfter 2 hours at RT
  7. extractionThe ethyl acetate is extracted off
  8. extractionthe water layer is extracted with ethyl acetate (4×)
  9. washThe combined organic layers are washed with water and with brine
  10. customdried
  11. filtrationfiltered
  12. washThe residue is washed with 20% ether/hexane (4× )

Sources & evidence

ORD record
ord-d71139e49b99450dbe9ec99489769ddf
Source dataset
uspto-grants-1983_09
Patent number
US04406690

Reaction notes

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