Sodium hydride → HCID 67528873, Verbindung

A solution of (E)-3-(tetrahydro-pyran-4-yl)-acrylic acid (prepared as described in PCT Publication WO 2005/101989 (A2,A3), 0.200 g, 1.28 mmol) in dry CH2Cl2 (5 mL) was treated with oxalyl chloride (0.110 mL, 0.00128 mol) and DMF (1 drop) at room temperature for 1 h. The volatiles were evaporated in vacuo (water bath temperature <30° C.). At the same time, a suspension of NaH (78.8 mg, 1.97 mmol, 60% dispersion in oil) in dry THF (3 mL) was treated portionwise with 3-nitro-2′-trifluoromethyl-biphenyl-4-ylamine (278 mg, 0.985 mmol, prepared as in STEP A above) and stirred at room temperature for 30 min. The residue was taken up in dry THF (2 mL) and slowly added to the NaH mixture. The resulting mixture was stirred at room temperature overnight, quenched with saturated aqueous NH4Cl (20 mL) and extracted with EtOAc (2×20 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 24-g Sepra Si 50 SPE column (Isco system: flow rate=20 mL/min; eluting with EtOAc/hexane, 5:95, v/v over 5 min and 5:95 to 40:60, v/v over 25 min) to yield (E)-N-(3-nitro-2′-trifluoromethyl-biphenyl-4-yl)-3-(tetrahydro-pyran-4-yl)-acrylamide as a yellow solid.

1. customThe volatiles were evaporated in vacuo (water bath temperature <30° C.)
2. stirringThe resulting mixture was stirred at room temperature overnight
3. customquenched with saturated aqueous NH4Cl (20 mL)
4. extractionextracted with EtOAc (2×20 mL)
5. dry with materialThe combined organic layers were dried over MgSO4
6. concentrationconcentrated in vacuo
7. customThe residue was purified on a 24-g Sepra Si 50 SPE column (Isco system
8. washeluting with EtOAc/hexane, 5:95, v/v over 5 min

ORD-Eintrag

ord-8642e7041ef04006a2ae8dd9b9ae69d7

Quelldatensatz

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08217060B2