Potassium Hydroxide → HCID 11412579, compound

12.60 g of 3-bromo-N-(4-fluorophenyl)propanamide (Example 152A, 39.94 mmol, 1 equivalent) were initially charged in 97.1 ml of dichloromethane, 11.19 g of 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6, 42.33 mmol, 1.06 equivalents) and 2.33 g of potassium hydroxide (41.54 mmol, 1.04 equivalents) were added and the mixture was stirred at RT overnight. 0.35 equivalents of 1,4,7,10,13,16-hexaoxacyclooctadecane and 0.35 equivalents of potassium hydroxide were then added and the mixture was stirred at RT overnight. Saturated aqueous ammonium chloride solution was then added and the mixture was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate and filtered, and the filtrate was concentrated and purified [column: Reprosil C18, 10 μm, Spring Column 470×50 mm; acetonitrile/water gradient; flow rate: 200 ml/min; 22° C.; wavelength: 210 nM]. This gave 3.46 g (38% of theory) of the title compound.

1. stirringthe mixture was stirred at RT overnight
2. extractionthe mixture was extracted three times with ethyl acetate
3. dry with materialThe combined organic phases were dried over sodium sulphate
4. filtrationfiltered
5. concentrationthe filtrate was concentrated
6. custompurified [column: Reprosil C18, 10 μm, Spring Column 470×50 mm; acetonitrile/water gradient; flow rate: 200 ml/min; 22° C.; wavelength: 210 nM]

ORD record

ord-be06df603d364f09a83fdf4db75f8fc6

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09126998B2