1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 18798270, compound

3,4-Difluorophenylacetic acid (3.61 g, 20.9 mmol) in oxalyl chloride (7.31 ml, 83.8 mmol) was refluxed for 4 hours. The solution was cooled to room temperature, concentrated under reduced pressure to give 3,4-difluorophenylacetyl chloride which was used without purification. To a well stirred solution of 3,4-difluorophenylacetyl chloride (2.21 g, 11.59 mmol) in THF (10 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (3.47 mL, 23.18 mmol) at room temperature and the solution was stirred for five minutes. Then methylisocyanoacetate (1.55 mL, 11.59 mmol) was added over a three minute period to the reaction mixture. After stirring for 18 hours at room temperature, the reaction mixture was partitioned between ether (100 mL) and water (50 mL). The organic layer was washed with 1N HCl (10 mL), water (15 mL) and saturated solution of sodium bicarbonate (15 mL), and dried over sodium sulfate. The solution was then filtered and concentrated. The residue was chromatographed (hexanes:EtOAc, 3:2) to yield 100 mg (3.4%) of the product; 1H-NMR (CDCl3) δ3.89 (s, 3H), 6.98 (s, 2H), 7.00-7.09 (m, 3H), 7.73 (s, 1H).

1. customwas used without purification
2. stirringAfter stirring for 18 hours at room temperature
3. customthe reaction mixture was partitioned between ether (100 mL) and water (50 mL)
4. washThe organic layer was washed with 1N HCl (10 mL), water (15 mL) and saturated solution of sodium bicarbonate (15 mL)
5. dry with materialdried over sodium sulfate
6. filtrationThe solution was then filtered
7. concentrationconcentrated
8. customThe residue was chromatographed (hexanes:EtOAc, 3:2)

ORD record

ord-9be2a64fff1e4d94916d8e3db22c2818

Source dataset

uspto-grants-2000_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06046331