Hydrochloric Acid → 4-[4-(1-aminoethyl)-3-methylphenyl]tetrahydro-2H-thiopyran-4-carbonitrile

HRID 419953Notes

Reaction equation

HRID 419953 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:15]#[N:16])[CH2:14][CH2:13][S:12][CH2:11][CH2:10]2)=[CH:5][C:4]=1[CH3:17])#[N:2].[CH3:18][Li].[BH4-].[Na+].Cl>C1COCC1.CCOCC>[NH2:2][CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:15]#[N:16])[CH2:10][CH2:11][S:12][CH2:13][CH2:14]2)=[CH:5][C:4]=1[CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 582984424-(4-Cyano-3-methylphenyl)tetrahydro-2H-thiopyran-4-carbonitrileHCID 178418348HCID 178418348, compound

Product 1

HCID 582984404-[4-(1-aminoethyl)-3-methylphenyl]tetrahydro-2H-thiopyran-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

4-(4-Cyano-3-methylphenyl)tetrahydro-2H-thiopyran-4-carbonitrile (983 mg, 4.06 mmol) is stirred in THF (40.0 mL) at −78° C. under nitrogen as a 1.6 M solution of methyllithium in Et2O is added slowly via syringe to the vessel. The contents are stirred for 3 hours at −20° C. before being quenched with MeOH (40.0 mL) and warmed to room temperature. NaBH4 (460 mg, 12.2 mmol) is slowly added at 0° C. in an ice bath and the mixture is warmed to room temperature and stirred for 16 hours. 1.0 N aqueous HCl is added until a pH of 3.0 is reached and the solvent is removed by rotary evaporator. To the residue is added concentrated aqueous HCl (3.0 mL) and the mixture is stirred for 16 hours. The contents are neutralized with 1.0 M aqueous NaOH and EtOAc (40.0 mL) is added. The layers are separated and the organic is dried with Na2SO4 and concentrated to a residue that is purified by silica get column chromatography (10% MeOH in DCM) (253 mg, 1.05 mmol, 26%).

Workup

  1. additionis added slowly via syringe to the vessel
  2. custombefore being quenched with MeOH (40.0 mL)
  3. temperaturewarmed to room temperature
  4. temperaturethe mixture is warmed to room temperature
  5. stirringstirred for 16 hours
  6. customthe solvent is removed by rotary evaporator
  7. additionTo the residue is added concentrated aqueous HCl (3.0 mL)
  8. stirringthe mixture is stirred for 16 hours
  9. additionis added
  10. customThe layers are separated
  11. dry with materialthe organic is dried with Na2SO4
  12. concentrationconcentrated to a residue that
  13. customis purified by silica
  14. customget column chromatography (10% MeOH in DCM) (253 mg, 1.05 mmol, 26%)

Sources & evidence

ORD record
ord-ea2fe6c0f90243779036d6c5eaccb848
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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