2-Chloropropane → 4-Amino-4-(1-(4-chlorophenyl)cyclobutyl]butan-1-ol

HRID 728282

Reaction equation

HRID 728282 reaction equation
C([Mg]Cl)(C)C.[Mg].ClC(C)C.Cl[CH2:12][CH2:13][CH2:14][OH:15].BrCC(Br)C.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2([C:32]#[N:33])[CH2:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1>O1CCCC1>[NH2:33][CH:32]([C:28]1([C:25]2[CH:24]=[CH:23][C:22]([Cl:21])=[CH:27][CH:26]=2)[CH2:29][CH2:30][CH2:31]1)[CH2:12][CH2:13][CH2:14][OH:15]

Participants

8

Reactant 6

HCID 63612-ChloropropaneHCID 65531,2-DibromopropaneHCID 123133-Chloro-1-propanolHCID 986211-(4-Chlorophenyl)cyclobutanecarbonitrileHCID 5462224Magnesium2×HCID 178418918HCID 178418918, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of isopropylmagnesium chloride [prepared by the reaction of magnesium (2.4 g) and 2-chloropropane (10 ml) in tetrahydrofuran (30 ml)] was added dropwise under argon at -20° C. to a solution of 3-chloropropan-1-ol (9.45 g) in tetrahydrofuran (100 ml). Magnesium (3.6 g) was added and the mixture was allowed to stand for twenty minutes and was then heated under reflux in the presence of 1,2-dibromopropane for 40 minutes. 1-(4-Chlorophenyl)cyclobutanecarbonitrile (8 g) was added and the mixture was heated under reflux for 16 hours. The mixture was cooled and the supernatant liquid decanted from excess magnesium metal and treated with sodium borohydride (3 g) and propan-2-ol (100 ml). The mixture was heated under reflux for 5 hours. The reaction mixture was cooled, added to water and excess concentrated hydrochloric acid was added. The resulting solution was washed with toluene, basified and extracted with toluene. The extracts were dried and evaporated to give a residue which was distilled in a Buchi Kugelrohr apparatus (140°/0.4 mm) to give 4-amino-4-[1-(4-chlorophenyl)-cyclobutyl]butan-1-ol.

Workup

  1. waitto stand for twenty minutes
  2. temperaturewas then heated
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 16 hours
  5. temperatureThe mixture was cooled
  6. customthe supernatant liquid decanted from excess magnesium metal
  7. additiontreated with sodium borohydride (3 g) and propan-2-ol (100 ml)
  8. temperatureThe mixture was heated
  9. temperatureunder reflux for 5 hours
  10. temperatureThe reaction mixture was cooled
  11. additionadded to water and excess concentrated hydrochloric acid
  12. additionwas added
  13. washThe resulting solution was washed with toluene
  14. extractionextracted with toluene
  15. customThe extracts were dried
  16. customevaporated
  17. customto give a residue which
  18. distillationwas distilled in a Buchi Kugelrohr apparatus (140°/0.4 mm)

Sources & evidence

ORD record
ord-a888cdfe24444f279b71c41bb67e5c5f
Source dataset
uspto-grants-1991_09
Patent number
US05047432

Linked notes

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