Tin atom → HCID 24956148, compound

HRID 1095567Notes

Reaction equation

HRID 1095567 reaction equation
Cl.[CH3:2][N:3]([CH3:32])[C:4]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:9][CH2:8][C:7]([C:10]2[NH:11][C:12]3[C:17]([C:18]=2[CH2:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:6][CH2:5]1.[Sn]>Br.O>[CH:20]1([CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[CH:7]2[CH2:6][CH2:5][C:4]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([N:3]([CH3:2])[CH3:32])[CH2:9][CH2:8]2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

5

Reactant 2

HCID 5352426Tin atomHCID 66783294HCID 66783294, compound

Product 1

HCID 24956148HCID 24956148, compound

Reagents, catalysts & solvents 2

HCID 260Hydrogen BromideSolventHCID 962WaterSolvent

Procedure

Ex. 40 (913 mg, 2.033 mmol) was dissolved in hydrogen bromide/glacial acetic acid (33% HBr, 46 ml). Tin powder (2.415 g, 20.344 mmol) was then added to the mixture in portions at room temperature in the course of 40 min and the mixture was stirred for a further 20 min. The mixture was then diluted with water (300 ml). The mixture was stirred at 5° C. for 1 h. The product precipitated out as the hydrobromide. This was filtered off and washed with water (2×5 ml). 1 N NaOH (50 ml) was added to the pink-coloured wet solid (5.7 g). The mixture was extracted with methylene chloride (3×30 ml). The combined organic phases were dried with Na2SO4 and filtered and the volatile constituents were removed completely in vacuo. A yellow solid (776 mg) remained. After separation of this mixture by chromatography [silica gel 60 (80 g); ethyl acetate (500 ml), ethyl acetate/methanol 20:1 (525 ml), ethyl acetate/methanol 5:1 (600 ml), ethyl acetate/methanol 2:1 (600 ml)], 4-(3-(cyclohexylmethyl)-1H-indol-2-yl)-N,N-dimethyl-1-phenylcyclohexanamine less polar diastereoisomer) (472 mg, contaminated) and the more polar diastereoisomer (269 mg, 32%, m.p.: 195-198° C.) were obtained as white solids.

Workup

  1. stirringThe mixture was stirred at 5° C. for 1 h
  2. customThe product precipitated out as the hydrobromide
  3. filtrationThis was filtered off
  4. washwashed with water (2×5 ml)
  5. addition1 N NaOH (50 ml) was added to the pink-coloured wet solid (5.7 g)
  6. extractionThe mixture was extracted with methylene chloride (3×30 ml)
  7. dry with materialThe combined organic phases were dried with Na2SO4
  8. filtrationfiltered
  9. customthe volatile constituents were removed completely in vacuo
  10. customAfter separation of this mixture by chromatography [silica gel 60 (80 g); ethyl acetate (500 ml), ethyl acetate/methanol 20:1 (525 ml), ethyl acetate/methanol 5:1 (600 ml), ethyl acetate/methanol 2:1 (600 ml)], 4-(3-(cyclohexylmethyl)-1H-indol-2-yl)-N,N-dimethyl-1-phenylcyclohexanamine less polar diastereoisomer) (472 mg, contaminated)
  11. customthe more polar diastereoisomer (269 mg, 32%, m.p.: 195-198° C.) were obtained as white solids

Sources & evidence

ORD record
ord-451881a072764b11aa8dc5e83855e373
Source dataset
uspto-grants-2012_03
Patent number
US08138187B2

Reaction notes

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