Diisopropylethylamine → 4-[(4-Fluorophenyl)sulfanyl]aniline

To a suspension of 2-methylisonicotinic acid (596 mg, 4.35 mmol) in dichloromethane (100 mL) are added N,N-diisopropylethylamine (1.15 mL, 6.72 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (1.91 g, 5.02 mmol). The mixture was stirred at room temperature for 1 h, after which benzyl 5-(4-fluorophenylthio)spiro[indoline-3,4′-piperidine]-1′-carboxylate (1.51 g, 3.37 mmol) is added. The reaction mixture is stirred at room temperature. After 18 h, additional 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (0.75 equiv) is added. After 2 days reaction time, the mixture is diluted with dichloromethane (300 mL), washed with saturated aqueous sodium hydrogen carbonate (100 mL) and brine (100 mL). The organic layer is dried over sodium sulphate, filtered and is concentrated under reduced pressure to give a brown oil. Purification of the crude by column chromatography on silica gel (heptane/ethyl acetate 40 to 100% as eluent) affords the desired product (1.09 g, 1.92 mmol, 57% yield) (HPLC-MS Method 2: retention time: 2.284 min, m/z 568.1).

1. stirringThe reaction mixture is stirred at room temperature
2. waitAfter 18 h
3. customAfter 2 days reaction time
4. washwashed with saturated aqueous sodium hydrogen carbonate (100 mL) and brine (100 mL)
5. dry with materialThe organic layer is dried over sodium sulphate
6. filtrationfiltered
7. concentrationis concentrated under reduced pressure
8. customto give a brown oil
9. customPurification of the crude by column chromatography on silica gel (heptane/ethyl acetate 40 to 100% as eluent)

ORD-Eintrag

ord-ff20066590bf400b9d3c66d90b46c44c

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09096599B2