Iodine → 1-[1-(3,4-Dichlorophenyl)cyclobutyl]-4-(2-methyl-1,3-dioxolan-2-yl)butylamine

HRID 728262Notes

Reaction equation

HRID 728262 reaction equation
Br[CH2:2][CH2:3][CH2:4][C:5]1([CH3:10])[O:9][CH2:8][CH2:7][O:6]1.II.[Mg].[Cl:14][C:15]1[CH:16]=[C:17]([C:22]2([C:26]#[N:27])[CH2:25][CH2:24][CH2:23]2)[CH:18]=[CH:19][C:20]=1[Cl:21].[BH4-].[Na+]>O1CCCC1.CC(O)C>[Cl:14][C:15]1[CH:16]=[C:17]([C:22]2([CH:26]([NH2:27])[CH2:2][CH2:3][CH2:4][C:5]3([CH3:10])[O:9][CH2:8][CH2:7][O:6]3)[CH2:25][CH2:24][CH2:23]2)[CH:18]=[CH:19][C:20]=1[Cl:21]

Participants

8

Reactant 5

HCID 807IodineHCID 5600542-(3-Bromopropyl)-2-methyl-1,3-dioxolaneHCID 4311764Sodium borohydrideHCID 5462224MagnesiumHCID 108571341-(3,4-Dichlorophenyl)-1-cyclobutane-carbonitrile

Product 1

HCID 538722161-[1-(3,4-Dichlorophenyl)cyclobutyl]-4-(2-methyl-1,3-dioxolan-2-yl)butylamine

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolvent2×HCID 8028TetrahydrofuranSolvent3×

Procedure

A portion (10 ml) of a solution of 2-(3-bromopropyl)-2-methyl-1,3-dioxolane (27.5 g) in dry tetrahydrofuran (70 ml) and an iodine crystal were added to a mixture of magnesium (3.5 g) and tetrahydrofuran (10 ml). The mixture was heated under reflux and a further portion (10 ml) added. When the reaction had been initiated the remaining solution was added over 40 minutes and reflux was maintained. 1-(3,4-Dichlorophenyl)cyclobutanecarbonitrile (18 g) and then dry tetrahydrofuran (10 ml) were added and the resulting solution heated under reflux for two hours. The solution was cooled, a slurry of sodium borohydride (5 g) and propan-2-ol (50 ml) was added and the mixture stirred at ambient temperature for 16 hours. Propan-2-ol (100 ml) was added and the mixture heated under reflux for 2.75 hours and then cooled and poured into ice/water (1000 g). The aqueous mixture was extracted with ether and the extract was dried and evaporated to give 1 -[1-(3,4-dichlorophenyl)cyclobutyl]-4-(2-methyl-1,3-dioxolan-2-yl)butylamine.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux
  3. additiona further portion (10 ml) added
  4. additionwas added over 40 minutes
  5. temperaturereflux
  6. temperaturewas maintained
  7. temperaturethe resulting solution heated
  8. temperatureunder reflux for two hours
  9. temperatureThe solution was cooled
  10. temperaturethe mixture heated
  11. temperatureunder reflux for 2.75 hours
  12. temperaturecooled
  13. extractionThe aqueous mixture was extracted with ether
  14. customthe extract was dried
  15. customevaporated

Sources & evidence

ORD record
ord-324bd48da747497488ede52c31410070
Source dataset
uspto-grants-1991_09
Patent number
US05047432

Reaction notes

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