Methyl iodide → 4-[(6-chloropyridin-3-yl)methyl]-7a-methyl-5,6,7,7a-tetrahydrofuro[3,2-b]pyridin-2(4H)-one

HRID 552901Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH:11]3[O:15][C:16](=[O:18])[CH:17]=[C:10]23)=[CH:4][CH:3]=1.[C:19]([Li])(C)(C)C.CI>O1CCCC1.CCCCC>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][C:11]3([CH3:19])[O:15][C:16](=[O:18])[CH:17]=[C:10]23)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: -78 °C

Procedure

43 mg (0.16 mmol) of 4-[(6-chloropyridin-3-yl)methyl]-5,6,7,7a-tetrahydrofuro[3,2-b]pyridin-2(4H)-one (1-2) are dissolved in 2.5 ml of tetrahydrofuran, the mixture is cooled to −78° C. and 96 μl (0.16 mmol) of a 1.7M solution of tert-butyllithium in pentane are added. After 30 minutes of stirring at −78° C., 15 μl (0.24 mmol) of methyl iodide are added, and the mixture is stirred at −78° C. for a further 30 min, warmed to room temperature and stirred at room temperature for a further 3 hours. Concentration under reduced pressure and purification of the residue by column chromatography on silica gel (silica gel 60, Merck, particle size: 0.04 to 0.063 mm) using the mobile phase ethyl acetate gives 16 mg (35% of theory) of 4-[(6-chloropyridin-3-yl)methyl]-7a-methyl-5,6,7,7a-tetrahydrofuro[3,2-b]pyridin-2(4H)-one.

Workup

stirringthe mixture is stirred at −78° C. for a further 30 min
temperaturewarmed to room temperature
stirringstirred at room temperature for a further 3 hours
concentrationConcentration
customunder reduced pressure and purification of the residue by column chromatography on silica gel (silica gel 60, Merck, particle size: 0.04 to 0.063 mm)

Sources & evidence

ORD record: ord-366d1a538c42425182011dfaefb20812
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07951951B2

Reaction notes

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