4-[6-(TRIBUTYLSTANNYL)-2-PYRIDINYL]MORPHOLINE synthesis

Yield:869901-24-6 7.2%

Reaction Conditions:

Stage #1: 4-(pyridin-2-yl)morpholinewith n-butyllithium;2-(N,N-dimethylamino)ethanol in hexane at -5 - 5; for 1.5 h;
Stage #2: tributyltin chloride in hexane at -78 - 20; for 2.5 h;
Stage #3: with water in hexane at 0;

Steps:

9.C.2

4-(6-Tributylstannanyl-pyridin-2-yl)-morpholineTo a solution of 2-dimethylaminoethanol (0.46 mL, 4.56 mmol) in hexane (7.0 mL, HPLC grade) cooled at -5⁰C was added drop wise n-BuLJ (1.60 M₁ 5.70 mL, 9.12 mmol) under nitrogen atmosphere. After 30 min at O⁰C₁ 4-pyridin-2-yl-morpholine (0.25 g, 1.52 mmol) in hexane (2.0 mL) was added drop wise. After stirring the reaction mixture for 1 h at 0-5⁰C, the reaction medium was cooled to -78⁰C followed by drop wise addition of tributyl tin chloride (1.03 mL, 3.70 mmol). The resulting reaction mixture was stirred at -78⁰C for 30 min and then allowed to stir at 0-5⁰C for 2h. The reaction mixture was then allowed to come to room temperature. After the completion of reaction (TLC monitoring), the reaction mass was cooled to O⁰C and water was added slowly. The aqueous phase was extracted with diethyl ether (3x 20 mL). The combined organic layers were dried over anhydrous Na₂SO₄, and evaporated to dryness. The crude residue was purified over silica gel (230-400 M) using EtOAc-Hexane (2:98) to provide the compound as yellow oil (0.050 g, 7.20%). MS: 455 (M+H)⁺.

References:

WO2007/148093,2007,A1 Location in patent:Page/Page column 65-66