Tributyltin Chloride → 2-Isopropoxy-6-(tributylstannyl)pyridine

HRID 634252Notes

Reaction equation

HRID 634252 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH:9]([CH3:11])[CH3:10])[N:3]=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].[NH4+].[Cl-]>C1COCC1>[CH:9]([O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Sn:21]([CH2:22][CH2:23][CH2:24][CH3:25])([CH2:26][CH2:27][CH2:28][CH3:29])[CH2:17][CH2:18][CH2:19][CH3:20])[N:3]=1)([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 15096Tributyltin ChlorideHCID 25517Ammonium ChlorideHCID 221807682-Bromo-6-isopropoxypyridineHCID 178418339Butyllithium

Product 1

HCID 683286192-Isopropoxy-6-(tributylstannyl)pyridineYield 50.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium pieces (200 mg) was added portion wise to 2-propanol (0.521 g, 6.35 mmol) and the reaction was stirred for 12 h at RT. To the above thick solution, 2,6-dibromo pyridine (1 g, 4.23 mmol, Aldrich) was added and the reaction was heated to 90° C. for 2 h. The mixture was cooled to RT and the solvent was removed. The crude residue was treated with ice water (10 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated. The residue was purified with silica gel column chromatography (Eluent: 0.5% EtOAc in petroleum ether) to give 2-bromo-6-isopropoxypyridine (600 mg, 66.5%) as a colorless liquid. MS (ESI, pos. ion) m/z: 216.0 (M+1); 1H-NMR (400 MHz, CDCl3): δ 7.38-7.34 (m, 1H), 6.99 (dd, J=7.2 Hz, J=4 Hz 1H), 6.60 (dd, J=8.0 Hz, J=4 Hz 1H). 5.28-5.25 (m, 1H), 1.32 (d, J=4.4 Hz, 6H). A solution of 2-bromo-6-isopropoxypyridine (1 g, 4.67 mmol) in dry THF (10 mL) was treated with n-BuLi (1.6M in hexane) (3.2 mL, 5.14 mmol) dropwise at −78° C. and the reaction was stirred at the same temperature for 30 min. Tributyl tin chloride (1.8 mL, 5.60 mmol, Aldrich) was added to the reaction at −78° C. and the reaction was stirred at the same temperature for 30 min. The mixture was treated with saturated NH4Cl solution (10 mL) and extracted with EtOAc (25 mL). The organic layer was dried over anhydrous Na2SO4, concentrated in vacuo. The residue was purified with silica gel column chromatography using (eluent: 100% petroleum ether) to give 2-isopropoxy-6-(tributylstannyl)pyridine (1 g, 50%) as a colorless liquid. 1H-NMR (300 MHz, CDCl3): δ 7.40-7.35 (m, 1H), 6.99 (dd, J=5.4, 4.5 Hz, 1H), 6.65 (dd, J=7.2, 0.6 Hz, 1H). 5.32-5.24 (m, 1H), 1.34-1.32 (m, 10H), 1.31-1.25 (m, 13H), 0.87-0.84 (m, 10H).

Workup

  1. stirringthe reaction was stirred at the same temperature for 30 min
  2. extractionextracted with EtOAc (25 mL)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified with silica gel column chromatography

Sources & evidence

ORD record
ord-efe0b911d0bc46a187f8db898dab62b7
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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