Oxalyl chloride → 4-[(4-Fluorophenyl)sulfanyl]aniline

Oxalyl chloride (1.68 mL, 19.59 mmol) and a catalytic amount of N,N-dimethylformamide are added to a pre-cooled (0° C.) suspension of 2-chloroisonicotinic acid (1.032 g, 6.55 mmol) in dichloromethane (350 mL). After the gas evolution ceases, the mixture is allowed to reach room temperature and is stirred for 1 h. The volatiles are then removed under reduced pressure. The residue obtained is dissolved in dichloromethane (150 mL) and the resulting solution is added to a pre-cooled (0° C.) solution of crude benzyl 5-(4-fluorophenylthio)spiro[indoline-3,4′-piperidine]-1-carboxylate (3.50 g, 42% wt/wt, 3.25 mmol) and N,N-diisopropylethylamine (1.65 mL, 9.64 mmol) in dichloromethane (400 mL). The reaction is stirred for 45 min at room temperature until complete conversion of the starting material is observed. The reaction mixture is washed with saturated aqueous sodium hydrogen carbonate (100 mL) and with brine (100 mL). The organic layer is dried over sodium sulphate, is filtered and is concentrated under reduced pressure. The yellow oil isolated is purified by column chromatography on silica gel (heptane/ethyl acetate 25 to 50% as eluent) to afford the desired product (1.58 g, 2.69 mmol, 83% yield) (HPLC-MS Method 2: retention time: 2.268 min, m/z 588.0).

1. temperaturea pre-cooled
2. customto reach room temperature
3. customThe volatiles are then removed under reduced pressure
4. customThe residue obtained
5. additionthe resulting solution is added to
6. stirringThe reaction is stirred for 45 min at room temperature until complete conversion of the starting material
7. washThe reaction mixture is washed with saturated aqueous sodium hydrogen carbonate (100 mL) and with brine (100 mL)
8. dry with materialThe organic layer is dried over sodium sulphate
9. filtrationis filtered
10. concentrationis concentrated under reduced pressure
11. customThe yellow oil isolated
12. customis purified by column chromatography on silica gel (heptane/ethyl acetate 25 to 50% as eluent)

ORD-Eintrag

ord-cf41593669414981a6bf5e82a388f954

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09096599B2