Sodium Hydroxide → HCID 24951512, compound

HRID 1095600Notes

Reaction equation

HRID 1095600 reaction equation
[CH3:1][NH:2][C:3]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:8][CH2:7][C:6]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=2)=[CH:15][CH:14]=[CH:13][CH:12]=3)=[CH:5][CH2:4]1.[Sn].[OH-].[Na+]>Br.C(Cl)Cl>[CH3:1][NH:2][C:3]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:8][CH2:7][CH:6]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH2:18][CH2:19][C:20]2[CH:21]=[CH:22][N:23]=[CH:24][CH:25]=2)=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 5352426Tin atomHCID 66782937HCID 66782937, compound

Product 1

HCID 24951512HCID 24951512, compound

Reagents, catalysts & solvents 2

HCID 260Hydrogen BromideSolventHCID 6344DichloromethaneSolvent

Procedure

Ex. 254 (350 mg, 0.86 mmol) was dissolved in hydrogen bromide/glacial acetic acid (33% HBr, 18 ml). Tin powder (1.02 g, 8.6 mmol) was then added to the mixture in portions at room temperature in the course of 40 min. A yellow suspension was formed. The mixture was stirred for a further 20 h. The mixture was then diluted with methylene chloride (50 ml) and rendered alkaline with 5 N sodium hydroxide solution (50 ml), while cooling with ice. The phases were separated. The aqueous phase was extracted with methylene chloride (3×30 ml). The combined organic phases were dried with Na2SO4 and then filtered. The volatile constituents of the filtrate were removed completely in vacuo. A pale yellow solid (534 mg) remained. This was separated by chromatography [silica gel 60 (50 g); ethyl acetate/methanol 4:1 (500 ml); methanol/ethyl acetate 3:2 (500 ml); 4:1 (500 ml)]. It was possible for N-methyl-1-phenyl-4-(3-(2-(pyridin-4-yl)ethyl)-1H-indol-2-yl)cyclohexanamine (less polar diastereoisomer) (178 mg, 50%, m.p.: 251-256° C.) and the more polar diastereoisomer (97 mg, 28%, m.p.: 224-227° C.) to be obtained in this way.

Workup

  1. customA yellow suspension was formed
  2. temperaturewhile cooling with ice
  3. customThe phases were separated
  4. extractionThe aqueous phase was extracted with methylene chloride (3×30 ml)
  5. dry with materialThe combined organic phases were dried with Na2SO4
  6. filtrationfiltered
  7. customThe volatile constituents of the filtrate were removed completely in vacuo
  8. customThis was separated by chromatography [silica gel 60 (50 g); ethyl acetate/methanol 4:1 (500 ml); methanol/ethyl acetate 3:2 (500 ml); 4:1 (500 ml)]
  9. customthe more polar diastereoisomer (97 mg, 28%, m.p.: 224-227° C.) to be obtained in this way

Sources & evidence

ORD record
ord-99416f3f5cb647059fd2b98e6882bada
Source dataset
uspto-grants-2012_03
Patent number
US08138187B2

Reaction notes

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