Triethylamine → (S)-(3-Hydroxypyrrolidin-1-yl)(tetrahydro-2H-pyran-4-yl)methanone

Temperature

3 °C

The (S)-pyrrolidin-3-ol hydrochloride (3.69 g, 29.9 mmol) and triethylamine (6.65 g, 9.16 mL, 65.7 mmol) were put in CH2Cl2 (15 mL). The suspension was cooled at ˜3° C. To this mixture, a solution of tetrahydro-pyran-4-carbonyl chloride (4.67 g, 29.9 mmol) in CH2Cl2 (15 mL) was added slowly. Then the resulting reaction mixture was stirred for 1.5 h at 3-10° C. The reaction mixture was then concentrated to give a powder. To this powder, addition of EtOAc (100 mL). The solid was filtered and washed with EtOAc. The recovered filtrate was then concentrated to give ((S)-3-hydroxy-pyrrolidin-1-yl)-(tetrahydro-pyran-4-yl)-methanone as beige powder. (6.77 g, 98% yield). 1H-NMR (400 MHz, Methanol-d4, 298 K): δ ppm 1.59-2.15 (m, 6H) 2.69-2.86 (m, 1H) 3.43-3.75 (m, 6H) 3.94-4.00 (m, 2H) 4.37-4.48 (m, 1H). LCMS: [M+H]+=199.9, Rt(6)=0.86 min

1. customThen the resulting reaction mixture
2. concentrationThe reaction mixture was then concentrated
3. customto give a powder
4. filtrationThe solid was filtered
5. washwashed with EtOAc
6. concentrationThe recovered filtrate was then concentrated

ORD record

ord-d222771fd16847c59d66588e87258860

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653092B2