2-(benzylaminoethoxy)tetrahydropyran synthesis

Yield:390401-24-8 99%

Reaction Conditions:

Stage #1: N-Benzylethanolaminewith methanesulfonic acid in dichloromethane at 10 - 16; for 0.166667 h;
Stage #2: 3,4-dihydro-2H-pyran in dichloromethane at 10 - 15; for 1.5 h;
Stage #3: with sodium hydroxide in dichloromethane at 5 - 10; for 1 h;

Steps:

2-Benzylaminoethanol (500.0 g, 3.31 mol) was dissolved in 1.7 L DCM and cooled to 10 °C. Methanesulfonic acid (349.5 g, 3.64 mol) was added within 45 min at 10-16 °C. After 10 min, 3,4-dihydro-2H-pyran (472.9 g, 5.62 mol) was added within 30 min at 10-15 °C. The solution was stirred for 1 h at 15 °C and was then added to a well stirred 3 N caustic solution (1.7 L, 4.91 mol) at 5-10 °C within 60 min. The phases were separated (2 min, 8°C) and the organic layer was concentrated in vacuum without drying.The oily yellow crude product (857 g) was purified by short path distillation at 3x10^"3 mbar and 118-125 °C to give compound 1 (777.0 g, 3.30 mol, 99 % yield, 96 area% LC purity).

References:

WO2012/85645,2012,A1 Location in patent:Page/Page column 36