Hydrochloric Acid → 4-Amino-4-(1-(4-chlorophenyl)cyclobutyl]butan-1-ol

HRID 728283Notes

Reaction equation

HRID 728283 reaction equation
Cl[CH2:2][CH2:3][CH2:4][OH:5].C([Mg]Cl)(C)C.[Mg].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2([C:23]#[N:24])[CH2:22][CH2:21][CH2:20]2)=[CH:15][CH:14]=1.[BH4-].[Na+].Cl>O1CCCC1.O.CC(O)C>[NH2:24][CH:23]([C:19]1([C:16]2[CH:15]=[CH:14][C:13]([Cl:12])=[CH:18][CH:17]=2)[CH2:20][CH2:21][CH2:22]1)[CH2:2][CH2:3][CH2:4][OH:5]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 123133-Chloro-1-propanolHCID 986211-(4-Chlorophenyl)cyclobutanecarbonitrileHCID 4311764Sodium borohydrideHCID 5462224MagnesiumHCID 178418918HCID 178418918, compound

Product 1

HCID 198237134-Amino-4-(1-(4-chlorophenyl)cyclobutyl]butan-1-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-chloropropan-1-ol (95 ml) in tetrahydrofuran cooled to below -5° C. was added over 30 minutes to a solution of isopropylmagnesium chloride [prepared from magnesium (30 g), 2-chloropropane (100 ml) and tetrahydrofuran (300 ml)]. Magnesium (36 g) was added and the mixture warmed to initiate the reaction which then had to be cooled. Tetrahydrofuran (300 ml) was then added and the mixture heated under reflux for 30 minutes. 1-(4-Chlorophenyl)cyclobutane-carbonitrile (90 g) was added and the mixture heated under reflux for 16 hours and then cooled. Sodium borohydride (30 g) and then propan-2-ol (250 ml) were added and the mixture heated under reflux for 5 hours. The reaction mixture was poured into water (1 l), and acidified with excess concentrated hydrochloric acid. The resulting acidic mixture was extracted with toluene. Removal of the toluene gave a residue which was triturated with ether to give a solid which was dried, basified and extracted with ether. The ether was removed by evaportion to give a residue which was distilled (180°/1 mm to 172°/0.8 mm) to give 4-amino-4-[1-(4-chlorophenyl)cyclobutyl]butan-1-ol.

Workup

  1. temperaturethe mixture warmed
  2. customthe reaction which
  3. temperatureto be cooled
  4. temperaturethe mixture heated
  5. temperatureunder reflux for 30 minutes
  6. temperaturethe mixture heated
  7. temperatureunder reflux for 16 hours
  8. temperaturecooled
  9. temperaturethe mixture heated
  10. temperatureunder reflux for 5 hours
  11. extractionThe resulting acidic mixture was extracted with toluene
  12. customRemoval of the toluene
  13. customgave a residue which
  14. customwas triturated with ether
  15. customto give a solid which
  16. customwas dried
  17. extractionextracted with ether
  18. customThe ether was removed by evaportion
  19. customto give a residue which
  20. distillationwas distilled (180°/1 mm to 172°/0.8 mm)

Sources & evidence

ORD record
ord-dfc5ffa5cacf4873a1fd9de2a01c8f72
Source dataset
uspto-grants-1991_09
Patent number
US05047432

Reaction notes

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