Hydrochloric Acid → 3-[1-(4-Pyridinylmethyl)-2-pyrrolidinyl]phenol

HRID 233016Notes

Reaction equation

HRID 233016 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:13][CH2:12][CH2:11][N:10]2[CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[CH:6]=[CH:7][CH:8]=1.B(Br)(Br)Br.Cl.C(=O)(O)[O-].[Na+]>ClCCl>[N:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:10]2[CH2:11][CH2:12][CH2:13][CH:9]2[C:5]2[CH:4]=[C:3]([OH:2])[CH:8]=[CH:7][CH:6]=2)=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 233612992-(3-Methoxyphenyl)-1-(4-pyridinylmethyl)pyrrolidine

Product 1

HCID 152932263-[1-(4-Pyridinylmethyl)-2-pyrrolidinyl]phenolYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

2-(3-Methoxyphenyl)-1-(4-pyridinylmethyl)pyrrolidine (5.70 g) was dissolved in dry dichloromethane (66 ml) and cooled to -78° C., under nitrogen. Boron tribromide in dichloromethane (1.0M solution, 66.0 ml) was added dropwise, and the reaction mixture was allowed to warm to ambient temperature overnight. The mixture was acidified with 5% hydrochloric acid to pH of 2 and then basified with saturated sodium bicarbonate solution to pH of 8. The layers were separated, and the aqueous phase was extracted with dichloromethane (3 times) and ether (1 time). The organic extracts were washed with brine, dried over anhydrous potassium carbonate, filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography (silica gel, 2% triethylamine/ether). The appropriate fractions were collected and concentrated to afford 1.60 g (30%) of product. Recrystallization from ether gave the analytical sample, mp 138° C.

Workup

  1. temperatureto warm to ambient temperature overnight
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with dichloromethane (3 times) and ether (1 time)
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over anhydrous potassium carbonate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customThe residue was purified by flash column chromatography (silica gel, 2% triethylamine/ether)
  9. customThe appropriate fractions were collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-9eef69c8c3a043869113aa118c1889b4
Source dataset
uspto-grants-1997_01
Patent number
US05591856

Reaction notes

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