Dichloromethane → HCID 86756540, compound

HRID 1532399Notes

Reaction equation

HRID 1532399 reaction equation
[C:1]1(=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C:12]([O-])(=O)[CH3:13].[NH4+:16].[C:17]([BH3-])#[N:18].[Na+].[OH-].[Na+].C(Cl)[Cl:24]>CO.O>[ClH:24].[ClH:24].[N:18]1[CH:17]=[CH:3][CH:2]=[CH:1][C:10]=1[CH2:12][CH2:13][C:1]1([NH2:16])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 107241-TetraloneHCID 14798Sodium HydroxideHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 86756540HCID 86756540, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

The tetralone 25 from the previous reaction (30.8 g, 130.9 mmol) was dissolved in methanol (650 mL) with stirring. Ammonium acetate (151.3 g, 1964 mmol) and sodium cyanoborohydride (41.1 g, 654 mmol) were added. The reaction vessel was flushed with nitrogen and a reflux condenser was installed. The reaction mixture was heated at reflux overnight. The solvent was removed in vacuo to give the crude product. This was dissolved in methylene chloride (600 mL) and water (300 mL). 1N Sodium hydroxide solution (1500 mL) was added to this biphasic mixture. The aqueous layer was removed and the organic layer was subsequently washed several times with dilute sodium hydroxide solution. The combined aqueous washes were extracted with fresh methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered, and the solvent removed in vacuo. The resulting residue was dissolved in ethyl ether and an excess of 1N hydrogen chloride in ethyl ether was added to precipitate the product. This material was triturated with additional portions of ethyl ether and filtered. The material was dried under vacuum. The -picolylmethyl--aminotetralin bis-hydrochloride 26 was obtained as a hygroscopic greenish powder (26.0 g, 83.5 mmol). MS: M+1=239; NMR(d6-DMSO): 8.71 (br, 3H), 8.62 (d, 1H), 8.47 (s, 1H), 7.97 (d, 1H), 7.63 (dd, 1H), 7.24-7.08 (m, 2H), 6.83 (dd, 1H), 6.03 (d, 1H), 3.68-3.52 (m, 1H), 3.44-3.35 (m, 2H), 3.12-2.83 (m, 2H), 2.71-2.58 (t app., 1H), 2.21-1.97 (m, 2H)

Workup

  1. customThe reaction vessel was flushed with nitrogen and a reflux condenser
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux overnight
  4. customThe solvent was removed in vacuo
  5. customto give the crude product
  6. customThe aqueous layer was removed
  7. extractionThe combined aqueous washes were extracted with fresh methylene chloride
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. customthe solvent removed in vacuo
  11. dissolutionThe resulting residue was dissolved in ethyl ether
  12. additionan excess of 1N hydrogen chloride in ethyl ether was added
  13. customto precipitate the product
  14. customThis material was triturated with additional portions of ethyl ether
  15. filtrationfiltered
  16. customThe material was dried under vacuum

Sources & evidence

ORD record
ord-3c5d1eb7be24422ab53987b5c7a8f303
Source dataset
uspto-grants-2001_03
Patent number
US06201025B1

Reaction notes

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