Phosgene → HCID 86672018, Verbindung

4-(Fluoromethyl)piperidin-4-ol hydrochloride (233 mg, 1.37 mmol) was suspended in dichloromethane (3 mL) followed by addition of DIPEA (0.6 mL, 3.4 mmol) and the slurry obtained added in portions over several minutes to a solution of phosgene (20W % in toluene, 0.75 mL) diluted into dichloromethane (5 mL) and the mixture was allowed to stir at this temperature for 15 minutes. The mixture was then concentrated and the residue partitioned with ethyl acetate and water. The organic solution was washed 0.5M hydrochloric acid, brine then dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (3:1 ethyl ether:hexanes) to give 4-(fluoromethyl)-4-hydroxypiperidine-1-carbonyl chloride (100 mg, 37% yield) as a colorless amorphous residue. GC-MS (EI) for C7H11FNO2Cl: 196 (M+).

1. customthe slurry obtained
2. concentrationThe mixture was then concentrated
3. customthe residue partitioned with ethyl acetate and water
4. washThe organic solution was washed 0.5M hydrochloric acid, brine
5. dry with materialthen dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by silica gel chromatography (3:1 ethyl ether:hexanes)

ORD-Eintrag

ord-c6d3afb8d7c343ba84b156cc757c0ba1

Quelldatensatz

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08637499B2