Pivaloyl chloride → HCID 12717062, compound

To an oven dried flask was charged with methyl 3-aminothiophene-2-carboxylate (30 g, 191 mmol) and pyridine (300 ml), followed by addition of pivaloyl chloride (25.3 g, 210 mmol) at room temperature. A mild exotherm occurred, and solid was formed. 10 min later, the reaction mixture was refluxed under N2 overnight (˜20 hr), and stirred at rt on weekend. Most of the solvent was removed on rotary vacuo. The brown residue was partitioned between 1N HCl and CH2Cl2(100 mL/150 mL). After seperation, the aqueous solution was extracted with CH2Cl2(100 mL), the combined organic layers were washed with brine (70 mL), dried on MgSO4, concentrated on rotary vacuo, the residue as a brown solid, was triturated with Et2O (30 mL), filtered and washed with Et2O (2×10 mL) to afford the expected product, N-(thiophen-3-yl)pivalamide (15.4 g, 50%) as an off white solid. 1H-NMR (400 MHz, CHLOROFORM-D) δ ppm 1.28 (s, 9 H) 6.98 (dd, J=5.16, 1.39 Hz, 1 H) 7.20 (dd, J=5.29, 3.27 Hz, 1 H) 7.57-7.66 (m, 2 H); Mass spec. C184.05 (MH+) calc. for C9H13NOS 183.07.

1. customTo an oven dried flask
2. customsolid was formed
3. temperature10 min later, the reaction mixture was refluxed under N2 overnight (˜20 hr)
4. customMost of the solvent was removed on rotary vacuo
5. customThe brown residue was partitioned between 1N HCl and CH2Cl2(100 mL/150 mL)
6. customAfter seperation
7. extractionthe aqueous solution was extracted with CH2Cl2(100 mL)
8. washthe combined organic layers were washed with brine (70 mL)
9. customdried on MgSO4
10. concentrationconcentrated on rotary vacuo
11. customthe residue as a brown solid, was triturated with Et2O (30 mL)
12. filtrationfiltered
13. washwashed with Et2O (2×10 mL)

ORD record

ord-7d6529f59b274e318ff4e664ef2814fd

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07470680B2