2-Iodothiophene → (4-Benzyloxy-1-thiophen-2-yl-cyclohexyl)dimethylamine

HRID 1349397Notes

Reaction equation

HRID 1349397 reaction equation
I[C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.C([Mg]Cl)(C)C.[CH2:12]([O:19][CH:20]1[CH2:25][CH2:24][C:23]([N:28]([CH3:30])[CH3:29])(C#N)[CH2:22][CH2:21]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:12]([O:19][CH:20]1[CH2:25][CH2:24][C:23]([N:28]([CH3:30])[CH3:29])([C:2]2[S:3][CH:4]=[CH:5][CH:6]=2)[CH2:22][CH2:21]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 189212-IodothiopheneHCID 25517Ammonium ChlorideHCID 210932404-Benzyloxy-1-dimethylaminocyclohexanecarbonitrileHCID 178418918HCID 178418918, compound

Product 1

HCID 12112391(4-Benzyloxy-1-thiophen-2-yl-cyclohexyl)dimethylamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

4.67 g of 2-iodothiophene were dissolved in 20 ml of tetrahydrofuran, and 7.26 ml of two molar isopropylmagnesium chloride solution in tetrahydrofuran were added dropwise under a nitrogen atmosphere, while cooling with an ice bath. After one hour, 2.50 g of 4-benzyloxy-1-dimethylaminocyclohexanecarbonitrile were added dropwise, dissolved in 10 ml of tetrahydrofuran. After stirring overnight at room temperature, the mixture was again cooled in an ice bath and 25 ml of cold ammonium chloride solution (20 wt. %) were added. The phases were separated and extracted three times using 40 ml of diethyl ether each time, and the combined organic phases were dried over sodium sulfate, filtered and concentrated. The resulting crude product (3.82 g) was separated on silica gel with diethyl ether. 1.59 g of the non-polar and 260 mg of the polar diastereoisomer of (4-benzyloxy-1-thiophen-2-yl-cyclohexyl)dimethylamine were obtained and, as described for Example 1, were converted into 1.11 g (Example 11) and 210 mg (Example 12) of the corresponding hydrochlorides using chlorotrimethylsilane and water in 2-butanone.

Workup

  1. temperaturewhile cooling with an ice bath
  2. temperaturethe mixture was again cooled in an ice bath
  3. customThe phases were separated
  4. extractionextracted three times
  5. dry with materialthe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting crude product (3.82 g) was separated on silica gel with diethyl ether

Sources & evidence

ORD record
ord-5283a245f4e940f99cc9dcb294cc8d57
Source dataset
uspto-grants-2007_05
Patent number
US07211694B2

Reaction notes

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