Tin atom → HCID 24956146, compound

HRID 1095566Notes

Reaction equation

HRID 1095566 reaction equation
[CH3:1][N:2]([CH3:29])[C:3]1([CH2:25][CH2:26][CH2:27][CH3:28])[CH2:8][CH2:7][C:6]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:14]=[CH:13][CH:12]=3)=[CH:5][CH2:4]1.[Sn]>Br.O>[CH2:18]([C:17]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][C:9]=1[CH:6]1[CH2:7][CH2:8][C:3]([CH2:25][CH2:26][CH2:27][CH3:28])([N:2]([CH3:1])[CH3:29])[CH2:4][CH2:5]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 2

HCID 5352426Tin atomHCID 66783005HCID 66783005, compound

Product 1

HCID 24956146HCID 24956146, compound

Reagents, catalysts & solvents 2

HCID 260Hydrogen BromideSolventHCID 962WaterSolvent

Procedure

Ex. 39 (438 mg, 1.133 mmol) was dissolved in hydrogen bromide/glacial acetic acid (33% HBr, 25 ml). Tin powder (1.345 g, 11.330 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 (100 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 moist yellow solid (4.0 g). The mixture was extracted with methylene chloride (3×30 ml). The combined organic phases were dried with Na2SO4 and filtered. The volatile constituents were removed completely in vacuo. An oil (425 mg) remained. After separation of this mixture by chromatography [silica gel 60 (40 g); ethyl acetate (500 ml), ethyl acetate/methanol 4:1 (750 ml)] 4-(3-benzyl-1H-indol-2-yl)-1-butyl-N,N-dimethylcyclohexanamine (less polar diastereoisomer, 210 mg, impure) and the more polar diastereoisomer (178 mg, 40%) was obtained as a yellow oil. The less polar diastereoisomer was purified further: Hot methanol (6 ml) was added and the mixture was left to stand at −10° C. overnight. The colourless solid which separated out (144 mg, 33%, melting point of 72-78° C. and 97-99° C.) was filtered off with suction and washed with cold methanol (2×0.5 ml).

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 moist yellow solid (4.0 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 (40 g); ethyl acetate (500 ml), ethyl acetate/methanol 4:1 (750 ml)] 4-(3-benzyl-1H-indol-2-yl)-1-butyl-N,N-dimethylcyclohexanamine (less polar diastereoisomer, 210 mg, impure) and the more polar diastereoisomer (178 mg, 40%)
  11. customwas obtained as a yellow oil
  12. customThe less polar diastereoisomer was purified further
  13. additionHot methanol (6 ml) was added
  14. waitthe mixture was left
  15. waitto stand at −10° C. overnight
  16. customThe colourless solid which separated out (144 mg, 33%, melting point of 72-78° C. and 97-99° C.)
  17. filtrationwas filtered off with suction
  18. washwashed with cold methanol (2×0.5 ml)

Sources & evidence

ORD record
ord-904cddf75ce24b28a913238853b61db5
Source dataset
uspto-grants-2012_03
Patent number
US08138187B2

Reaction notes

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