Cesium fluoride → 4-[5-(1-Methyl-2-pyrrolidinyl)-3-pyridinyl]phenol

HRID 1941270Notes

Reaction equation

HRID 1941270 reaction equation
[Si]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]([CH:21]3[CH2:25][CH2:24][CH2:23][N:22]3[CH3:26])[CH:18]=[N:19][CH:20]=2)=[CH:11][CH:10]=1)(C(C)(C)C)(C)C.[F-].[Cs+]>CO>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[C:17]([CH:21]3[CH2:25][CH2:24][CH2:23][N:22]3[CH3:26])[CH:18]=[N:19][CH:20]=2)=[CH:13][CH:14]=1

Participants

4

Reactant 2

HCID 25953Cesium fluorideHCID 196943125-(4-Tert-butyldimethylsilyloxyphenyl)-3-(1-methyl-2-pyrrolidinyl)pyridine

Product 1

HCID 196943114-[5-(1-Methyl-2-pyrrolidinyl)-3-pyridinyl]phenolYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The above-described pyridine derivative (750 mg, 2.04 mmol) was dissolved in methanol (40 mL) and cesium fluoride (620 mg, 4.08 mmol) was added. The stirred mixture was heated at reflux for 18 h under inert atmosphere. After cooling the solvent was removed in vacuo and the resulting oil was dissolved in ethyl acetate (50 mL). This was washed with water (20 mL), brine (20 mL), dried (MgSO4) and concentrated. The crude material was chromatographed on "flash" silica gel with ethyl acetate:hexane (1:2) to 10% methanol:ethyl acetate as eluant to afford 5-(4-hydroxyphenyl)-3-(1-methyl-2-pyrrolidinyl)pyridine 480 mg, 93% as a colorless foam, 1H NMR (CDCl3, 300 MHz): δ8.66 (d, J=2 Hz, 1H), 8.43 (d, J=2 Hz, 1H), 7.90 (s, 1H), 7.32 (d, J=9 Hz, 2H), 6.81 (d, J=9 Hz, 2H), 3.33 (t, J=8 Hz, 1H), 3.22 (t, J=8 Hz, 1H), 2.41 (m, 1H), 2.28 (s, 3H), 2.10 (m, 2H), 1.93 (m, 2H).

Workup

  1. temperatureThe stirred mixture was heated
  2. temperatureat reflux for 18 h under inert atmosphere
  3. temperatureAfter cooling the solvent
  4. customwas removed in vacuo
  5. dissolutionthe resulting oil was dissolved in ethyl acetate (50 mL)
  6. washThis was washed with water (20 mL), brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe crude material was chromatographed on "flash" silica gel with ethyl acetate:hexane (1:2) to 10% methanol

Sources & evidence

ORD record
ord-36e599fd65324f09a5737e32bb1c9646
Source dataset
uspto-grants-1997_12
Patent number
US05703100

Reaction notes

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