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

HRID 575062Notes

Reaction equation

HRID 575062 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×

Procedure

This compound was prepared according to a procedure similar to that described in Procedure B. To a solution of 2.5 M n-butyllithium in hexanes (3.91 ml) in THF (3 ml) at −78° C. was added dropwise ethynyl(trimethyl)silane (1.28 ml, 9.01 mmol). The reaction was stirred at −78° C. for 10 min before addition of a solution of 5,6-dihydro-7H-cyclopenta[b]pyridin-7-one (1 g, 7.51 mmol) in THF (7 ml). The reaction mixture was stirred and allowed to warm up to RT for 3 hr. The mixture was then diluted with water and the volatiles removed. The product was extracted with CHCl3:IPA (2:1 ratio, 2×25 ml). The organic phase was washed with water (20 mL) followed by brine (20 mL); dried over (Na2SO4), and the solvent removed in vacuo. Purification by column chromatography (25 g Isolute column, 100% DCM to 5% MeOH in DCM) followed by the second column chromatography (30% EtOAc-heptane) gave the title compound: 1H NMR (500 MHz, CDCl3) δ 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: 459.95 (M+H)+.

Workup

  1. customThis compound was prepared
  2. customthe volatiles removed
  3. extractionThe product was extracted with CHCl3:IPA (2:1 ratio, 2×25 ml)
  4. washThe organic phase was washed with water (20 mL)
  5. dry with materialdried over (Na2SO4)
  6. customthe solvent removed in vacuo
  7. customPurification by column chromatography (25 g Isolute column, 100% DCM to 5% MeOH in DCM)

Sources & evidence

ORD record
ord-c889e9aaa4d84dd0adb6fef2ce835e55
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

Loading…