Ethyl Bromide → HCID 20041061, compound

HRID 1762463Notes

Reaction equation

HRID 1762463 reaction equation
CC1N=CSC=1.C([Mg]Br)C.[Mg].C(Br)C.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2(C#N)[CH2:25][CH2:24][CH2:23]2)=[CH:18][CH:17]=1.[OH-].[Na+].Cl.ClC1C=CC(C2([C:42]([C:44]3[S:45][CH:46]=[C:47]([CH3:49])[N:48]=3)=[NH:43])CCC2)=CC=1.[BH4-].[Na+]>CCOCC.O.C1(C)C=CC=CC=1.O1CCCC1>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]2([NH:43][CH2:42][C:44]3[S:45][CH:46]=[C:47]([CH3:49])[N:48]=3)[CH2:23][CH2:24][CH2:25]2)=[CH:20][CH:21]=1

Participants

13

Reactant 8

HCID 6332Ethyl BromideHCID 127484-MethylthiazoleHCID 14798Sodium Hydroxide2×HCID 986211-(4-Chlorophenyl)cyclobutanecarbonitrileHCID 4311764Sodium borohydrideHCID 5462224MagnesiumHCID 20041056HCID 20041056, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 20041061HCID 20041061, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-methylthiazole (4.95 g) in ether (5 ml) was added to ethylmagnesium bromide prepared under nitrogen from magnesium turnings (1.2 g) and ethyl bromide (5.5 g) in ether (40 ml). A yellow precipitate was formed which dissolved when the ether was replaced by tetrahydrofuran (70 ml). 1-(4-Chlorophenyl)cyclobutanecarbonitrile (6.0 g) was added and the solvent replaced by toluene and the mixture heated at 90° C. for two hours. Water and 2N sodium hydroxide solution were added and the reaction mixture extracted with ether. The extract was dried and the solvents removed by evaporation. The residue was dissolved in ether and hydrogen chloride gas was passed into the solution to give a pale yellow solid which is believed to be [1-(4-chlorophenyl)cyclobutyl](4-methylthiazol2-yl)methanimine hydrochloride. This salt was heated at 95° C. for two hours with a solution of sodium borohydride (2 g) in diethyleneglycoldimethylether (100 ml). Water and 2N sodium hydroxide solution were added and the reaction mixture extracted with ether. The extract was dried and the solvents removed by evaporation. The residue was dissolved in ether and hydrogen chloride gas was passed into the solution to give a yellow solid. This solid was converted into the free base which was purified by column chromatography on a florisil column eluted with a mixture of ether and cyclohexane to give [1-(4-chlorophenyl)cyclobutyl](4-methylthiazol-2-yl)methylamine which was converted into a hydrochloride salt [m.p. 230°-232° C. (dec)]containing 1.5 moles of hydrochloride by dissolving the free base in ether and passing hydrogen chloride gas through the solution.

Workup

  1. customA yellow precipitate was formed which
  2. extractionthe reaction mixture extracted with ether
  3. customThe extract was dried
  4. customthe solvents removed by evaporation
  5. dissolutionThe residue was dissolved in ether
  6. customto give a pale yellow solid which
  7. extractionthe reaction mixture extracted with ether
  8. customThe extract was dried
  9. customthe solvents removed by evaporation
  10. dissolutionThe residue was dissolved in ether
  11. customto give a yellow solid
  12. customwas purified by column chromatography on a florisil column
  13. washeluted with a mixture of ether and cyclohexane

Sources & evidence

ORD record
ord-49ddd3926d85416580a3b7c3a802e3b6
Source dataset
uspto-grants-1989_05
Patent number
US04833143

Reaction notes

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