Trimethylsilylacetylene → 7-ethynyl-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ol

HRID 1398528Notes

Reaction equation

HRID 1398528 reaction equation
[CH2:1]([Li])[CH2:2]CC.C([Si](C)(C)C)#C.[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]2[CH2:18][CH2:19][C:20](=[O:21])[C:13]=12>C1COCC1.O>[C:1]([C:20]1([OH:21])[C:13]2=[N:12][CH:17]=[CH:16][CH:15]=[C:14]2[CH2:18][CH2:19]1)#[CH:2]

Participants

6

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 110407455H,6H,7H-cyclopenta[b]pyridin-7-oneHCID 178418339Butyllithium

Product 1

HCID 866695787-ethynyl-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of n-butyllithium (2.5M in hexane, 19.5 ml, 48.75 mmol) in THF (15 ml) at −78° C. was added dropwise ethynyl(trimethyl)silane (6.41 ml, 45.06 mmol). The reaction was stirred at −78° C. for 20 minutes and then a solution of 5,6-dihydro-7H-cyclopenta[b]pyridin-7-one (5 g, 7.51 mmol) in THF (25 mL) was added. The reaction mixture was stirred at −78° C. to RT for 4 hr. The mixture was then diluted with water and the volatiles removed in vacuo. The product was extracted with CHCl3:IPA (2:1 ratio, 3×30 ml) and the organic phase was washed with water (30 mL), brine (30 mL); dried over Na2SO4, filtered and concentrated in vacuo. Purification by column chromatography (Biotage), eluting with 0-5% MeOH-DCM followed by another column chromatography purification with 30% EtOAc/heptanes gave the title compound; 1H NMR (500 MHz, CDCl3) 2.49 (1H, ddd, J=13.44, 8.24, 6.07 Hz), 2.63-2.76 (2H, m), 2.90-3.02 (1H, m), 3.03-3.13 (1H, m), 3.42 (1H, s), 7.22 (1H, dd, J=7.57, 4.89 Hz), 7.62 (1H, d, J=7.57 Hz), 8.51 (1H, d, J=4.73 Hz); LC-MS: m/z=+159.9 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. to RT for 4 hr
  2. customthe volatiles removed in vacuo
  3. extractionThe product was extracted with CHCl3:IPA (2:1 ratio, 3×30 ml)
  4. washthe organic phase was washed with water (30 mL), brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography (Biotage)
  9. washeluting with 0-5% MeOH-DCM
  10. customfollowed by another column chromatography purification with 30% EtOAc/heptanes

Sources & evidence

ORD record
ord-b06bc45e9d2a4bcd9be736fc11a52a05
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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