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

HRID 1995847Notes

Reaction equation

HRID 1995847 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° & 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 separated off, and the water layer is extracted with ethyl acetate (4X). The combined organic layers are washed with water and with brine, dried, filtered and rotoevaporated. The residue is washed with 20% ether/hexane (4X). 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. customThe ethyl acetate is separated off
  8. extractionthe water layer is extracted with ethyl acetate (4X)
  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 (4X)

Sources & evidence

ORD record
ord-7bfc2f45b81b4f31946a22ba3dcb72ae
Source dataset
uspto-grants-1983_09
Patent number
US04406689

Reaction notes

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