Water → 5-bromo-N-(4,4-dimethylcyclohexyl)-2,3-dihydro-1H-inden-1-amine

HRID 70306

Reaction equation

HRID 70306 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=O)[CH2:6][CH2:5]2.[CH3:12][C:13]1([CH3:20])[CH2:18][CH2:17][CH:16]([NH2:19])[CH2:15][CH2:14]1.[BH3-]C#N.[Na+].O>CCO.CO.C1COCC1.CC(O)=O.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([NH:19][CH:16]1[CH2:17][CH2:18][C:13]([CH3:20])([CH3:12])[CH2:14][CH2:15]1)[CH2:6][CH2:5]2

Participants

8

Reactant 4

HCID 962WaterHCID 4210544,4-Dimethylcyclohexan-1-amineHCID 5206955-Bromo-1-indanoneHCID 5003444Sodium cyanoborohydride2×

Product 1

HCID 582762435-bromo-N-(4,4-dimethylcyclohexyl)-2,3-dihydro-1H-inden-1-amine

Reagents, catalysts & solvents 3

HCID 178460666HCID 178460666, compoundCatalystHCID 702EthanolSolventHCID 18673759MeOH THF HOAcSolvent

Procedure

To a slurry of 5-bromo-1-indanone (0.449 g; 2.13 mmol) and 4,4-dimethylcyclohexanamine (2.24 mmol; Note 1) under N2 was added Ti(OiPr)4 (0.94 mL; 3.2 mmol) via syringe. The mixture was stirred 16 h at room temperature, a solution of NaBH3CN (0.134 g; 2.13 mmol) in EtOH (5 mL) was added and stirring continued an additional 4 h. Water was added and the whole was filtered through a pad of Celite (washed 2×EtOH, 2×THF). Combine filtrate and washings were concentrated in vacuo, the residue was taken up in CH2Cl2 and stirred under 1N NaOH for 1 h. Layers were separated, the aqueous layer was extracted with CH2Cl2 (×2), combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in MeOH/THF/HOAc (15/3/0.3 mL respectively), NaBH3CN (0.134 g; 2.13 mmol) was added and the mixture was stirred at room temperature overnight. After 17 h the mixture was concentrated in vacuo, partitioned between CH2Cl2/1N NaOH and the layers were separated. The aqueous layer was extracted with CH2Cl2 (×2), combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes; Note 2), affording the title compound as a pale yellow syrup. LC/MS (method A) tR 1.79 min; m/z 322, 324 (M+H, Br isotopes).

Workup

  1. stirringstirring
  2. waitcontinued an additional 4 h
  3. filtrationthe whole was filtered through a pad of Celite (washed 2×EtOH, 2×THF)
  4. concentrationCombine filtrate and washings were concentrated in vacuo
  5. stirringstirred under 1N NaOH for 1 h
  6. customLayers were separated
  7. extractionthe aqueous layer was extracted with CH2Cl2 (×2)
  8. washcombined organics were washed (water, brine)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. additionwas added
  12. stirringthe mixture was stirred at room temperature overnight
  13. concentrationAfter 17 h the mixture was concentrated in vacuo
  14. custompartitioned between CH2Cl2/1N NaOH
  15. customthe layers were separated
  16. extractionThe aqueous layer was extracted with CH2Cl2 (×2)
  17. washcombined organics were washed (water, brine)
  18. dry with materialdried over Na2SO4
  19. concentrationconcentrated in vacuo
  20. customThe residue was purified by flash chromatography (EtOAc/hexanes; Note 2)

Sources & evidence

ORD record
ord-ac926becbc134706b0a2d10601e2f67a
Source dataset
uspto-grants-2014_09
Patent number
US08822518B2

Linked notes

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