Hydrochloric Acid → HCID 86718582, compound

HRID 1480623Notes

Reaction equation

HRID 1480623 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]([C:19]1[CH:20]=[C:21]([C:28]2[CH:29]=[N:30][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:32][CH:33]=2)[C:22]([OH:27])=[C:23]([CH:26]=1)[CH:24]=O)([CH3:18])([CH3:17])[CH3:16].[NH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1.C(O)C.[ClH:47]>O1CCCC1>[ClH:47].[C:15]([C:19]1[CH:20]=[C:21]([C:28]2[CH:29]=[N:30][C:31]([C:34]([F:36])([F:35])[F:37])=[CH:32][CH:33]=2)[C:22]([OH:27])=[C:23]([CH2:24][N:38]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)[CH:26]=1)([CH3:17])([CH3:16])[CH3:18]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 8082Piperidine2×HCID 5049666Sodium triacetoxyborohydride2×HCID 86718581HCID 86718581, compound

Product 1

HCID 86718582HCID 86718582, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium triacetoxyborohydride (0.30 g, 1.4 mmol) was added to a solution of 5-(tert-butyl)-2-hydroxy-3-(6-(trifluoromethyl)pyridin-3-yl)benzaldehyde (0.35 g, 1.1 mmol) and piperidine (0.13 mL, 1.3 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature under nitrogen for 16 hours. Additional piperidine (013 mL, 1.3 mmol) and sodium triacetoxyborohydride (0.30 g, 1.4 mmol) were added and the reaction was stirred under nitrogen for 4 hours. The reaction was partitioned between ethyl acetate (25 mL) and saturated aqueous sodium bicarbonate solution (25 mL). The organic phase was dried with sodium sulfate, filtered and concentrated under reduced pressure to give a yellow syrup. The product was purified using flash chromatography on silica eluting with a solvent gradient of 0 to 100% ethyl acetate in hexanes to give a yellow syrup which was dissolved in 1.25 M hydrochloric acid in ethanol (10 mL, 12.5 mmol). The mixture stood for 20 minutes and was concentrated under reduced pressure to give a white solid which was triturated with diethyl ether (10 mL) and the solid was filtered off to afford 4-(tert-butyl)-2-(piperidin-1-ylmethyl)-6-(6-(trifluoromethyl)pyridin-3-yl)phenol hydrochloride (0.29 g, 62% yield) as a white solid.

Workup

  1. stirringthe reaction was stirred under nitrogen for 4 hours
  2. customThe reaction was partitioned between ethyl acetate (25 mL) and saturated aqueous sodium bicarbonate solution (25 mL)
  3. dry with materialThe organic phase was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give a yellow syrup
  7. customThe product was purified
  8. customto give a yellow syrup which
  9. waitThe mixture stood for 20 minutes
  10. concentrationwas concentrated under reduced pressure
  11. customto give a white solid which
  12. customwas triturated with diethyl ether (10 mL)
  13. filtrationthe solid was filtered off

Sources & evidence

ORD record
ord-489a9db12cda423fb10bf641612115e0
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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