Cyclopentanone → HCID 59265957, compound

HRID 646629Notes

Reaction equation

HRID 646629 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[C:9]1(=[O:14])[CH2:13][CH2:12][CH2:11][CH2:10]1>C(OCC)C>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([C:9]2([OH:14])[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:3][CH:4]=1

Participants

4

Reactant 2

HCID 8452CyclopentanoneHCID 27344145-Bromo-2-chloropyridine

Product 1

HCID 59265957HCID 59265957, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-20 °C

Procedure

5-Bromo-2-chloropyridine (3.0 g, 15.6 mmol) was dissolved in diethyl ether (100 mL) in an oven-dried, nitrogen-flushed 250 mL round bottomed flask and cooled in a dry ice/acetone bath under nitrogen. n-BuLi (1.05 g, 16.4 mmol, 6.6 mL of a 2.5 M solution in hexanes) was added via syringe and the orange heterogenous mixture allowed to stir for 1 hour. Cyclopentanone (1.3 g, 15.6 mmol) was added via syringe and the mixture allowed to warm to −20° C. before being quenched with 1N HCl. The mixture was extracted with EtOAc and the organic extract washed with sat. NaHCO3. The NaHCO3 wash was used to neutralize the first aqueous layer and the combined aqueous layers were extracted with additional EtOAc and the combined organic layers dried (Na2SO4), filtered, concentrated and purified by flash silica gel chromatography (hexanes:EtOAc; 2:1) to give 1-(6-chloro-pyridin-3-yl)cyclopentanol (2.33 g, 76%) as an off white solid: mp 92-93° C., LC/MS (ESI) m/z 197, 1H NMR (300 MHz, CDCl3) δ 8.50 (d, 1H, J=2.4 Hz), 7.77 (dd, 1H, J=8.4, 2.4 Hz), 7.28 (d, 1H, J=8.4 Hz), 2.05-1.80 (m, 8H), 1.60 (s, 1H, OH).

Workup

  1. customflushed 250 mL round bottomed flask
  2. temperaturecooled in a dry ice/acetone bath under nitrogen
  3. additionn-BuLi (1.05 g, 16.4 mmol, 6.6 mL of a 2.5 M solution in hexanes) was added via syringe
  4. custombefore being quenched with 1N HCl
  5. extractionThe mixture was extracted with EtOAc
  6. extractionthe organic extract
  7. washwashed with sat. NaHCO3
  8. washThe NaHCO3 wash
  9. extractionthe combined aqueous layers were extracted with additional EtOAc
  10. dry with materialthe combined organic layers dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. custompurified by flash silica gel chromatography (hexanes:EtOAc; 2:1)

Sources & evidence

ORD record
ord-07d30fb46c394d8aaa2fff5ef91c6b8b
Source dataset
uspto-grants-2010_04
Patent number
US07705156B2

Reaction notes

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