Ethanol → HCID 86718595, compound

HRID 1480633Notes

Reaction equation

HRID 1480633 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH2:15]([N:17]([CH2:21][CH3:22])[CH2:18][CH2:19][NH2:20])[CH3:16].[C:23]([C:27]1[CH:28]=[C:29]([C:36]2[CH:37]=[N:38][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:40][CH:41]=2)[C:30]([OH:35])=[C:31]([CH:34]=1)[CH:32]=O)([CH3:26])([CH3:25])[CH3:24].[BH4-].[Na+].[Cl-:48].[NH4+].C(O)C>O1CCCC1.Cl>[ClH:48].[ClH:48].[C:23]([C:27]1[CH:28]=[C:29]([C:36]2[CH:37]=[N:38][C:39]([C:42]([F:43])([F:44])[F:45])=[CH:40][CH:41]=2)[C:30]([OH:35])=[C:31]([CH2:32][NH:20][CH2:19][CH2:18][N:17]([CH2:21][CH3:22])[CH2:15][CH3:16])[CH:34]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

9

Reactant 6

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 60993N,N-DiethylethylenediamineHCID 4311764Sodium borohydride2×HCID 5049666Sodium triacetoxyborohydrideHCID 86718581HCID 86718581, compound

Product 1

HCID 86718595HCID 86718595, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium triacetoxy borohydride (590 mg, 2.79 mmol) was added to a solution of N,N-diethylethylenediamine (0.37 mL, 2.63 mmol) and 5-(tert-butyl)-2-hydroxy-3-(6-(trifluoromethyl)pyridin-3-yl)benzaldehyde (Example 47, Step 1) (0.50 g, 1.55 mmol) in tetrahydrofuran (15 mL) and the reaction mixture stirred at room temperature under nitrogen for 16 hours. Progress of the reaction was monitored by LC/MS and showed both product and starting material. A reaction aliquot was treated with sodium borohydride and the LC/MS showed only product. Therefore, the reaction solvent was removed under reduced pressure and the residue re-dissolved in methanol (15 mL) and sodium borohydride (286 mg, 7.74 mmol) added. The reaction mixture was stirred at room temperature for 10 minutes and then saturated aqueous ammonium chloride solution (1.0 mL) added. The reaction mixture was partitioned between saturated aqueous ammonium chloride solution and ethyl acetate. The organic phase was separated, dried (Na2SO4), filtered and the solvent was removed under reduced pressure. The residue was purified using flash chromatography on silica eluting with a solvent gradient of 0 to 100% (1% ammonium hydroxide, 10% methanol, 89% methylene chloride) in methylene chloride. The product was dissolved in a 1.25 M solution of hydrochloric acid in ethanol (5 mL, 6.3 mmol), the mixture stirred for 30 minutes then concentrated under reduced pressure. The product was triturated with diethyl ether to give 4-(tert-butyl)-2-(((2-(diethylamino)ethyl)amino)methyl)-6-(6-(trifluoromethyl)pyridin-3-yl)phenol dihydrochloride (190 mg, 25% yield) as a white powder.

Workup

  1. customTherefore, the reaction solvent was removed under reduced pressure
  2. dissolutionthe residue re-dissolved in methanol (15 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 10 minutes
  4. customThe reaction mixture was partitioned between saturated aqueous ammonium chloride solution and ethyl acetate
  5. customThe organic phase was separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was purified
  10. stirringthe mixture stirred for 30 minutes
  11. concentrationthen concentrated under reduced pressure
  12. customThe product was triturated with diethyl ether

Sources & evidence

ORD record
ord-f4f69ae1ea004046a65f0254814aa810
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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