Water → 3-(5-Tributylstannanyl-thiazol-2-yl)-pyridine
Reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1.[Li]CCCC.[CH2:17]([Sn:21](Cl)([CH2:26][CH2:27][CH2:28][CH3:29])[CH2:22][CH2:23][CH2:24][CH3:25])[CH2:18][CH2:19][CH3:20].O>C1COCC1>[CH2:26]([Sn:21]([CH2:17][CH2:18][CH2:19][CH3:20])([CH2:22][CH2:23][CH2:24][CH3:25])[C:5]1[S:1][C:2]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)=[N:3][CH:4]=1)[CH2:27][CH2:28][CH3:29]Participants
Conditions
- Temperature
- -78 °C
Procedure
To a stirred solution of 3-thiazol-2-yl-pyridine (J. Med. Chem. 2005, 48, 224) (927 mg, 5.71 mmol) in dry THF (30 mL) cooled at −78° C. under an inert atmosphere was added n-BuLi (2.5M in hexanes) (2.75 mL, 6.87 mmol) dropwise. After stirring at −78° C. for 45 mins, tributyltin chloride (1.86 mL, 6.87 mmol) was added. The mixture was allowed to warm to 0° C. over 90 mins, then treated with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and evaporated under reduced pressure before purification by column chromatography on SiO2 using combiflash Companion®, eluting with cyclohexane/ethyl acetate 100/0 to 82/18 to afford 3-(5-tributylstannanyl-thiazol-2-yl)-pyridine as a colourless oil (955 mg, 37%). 1H NMR (DMSO-d6, 300 MHz) δ=9.11 (m, 1H), 8.62 (dd, J=4.77-1.52 Hz, 1H), 8.28 (m, 1H), 7.90 (s, 1H), 7.50 (dd, J=8.0-4.8 Hz, 1H), 1.52 (m, 6H), 1.28 (m, 6H), 1.13 (m, 6H), 0.84 (t, J=7.2 Hz, 9H).
Workup
- temperatureto warm to 0° C. over 90 mins
- extractionextracted with ethyl acetate
- washThe combined organic layers were washed with brine
- dry with materialdried over MgSO4
- filtrationfiltered
- customevaporated under reduced pressure before purification by column chromatography on SiO2 using combiflash Companion®
- washeluting with cyclohexane/ethyl acetate 100/0 to 82/18
Sources & evidence
- ORD record
- ord-7207b0e0828847e08aa25e24b082f858
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08962665B2
Reaction notes
Loading…