Diisopropylethylamine → HCID 18761445, compound

The achiral 2-(4-benzyloxy-2-nitrophenyl)ethyl chloride compound (0.500 g, 1.71 mmol) was dissolved in freezer-chilled THF (30 mL) and PtO2 (0.150 g) was added. The reaction was stirred while degassing under vacuum, followed by exposure to hydrogen gas. The degas/hydrogen exposure cycle was repeated 3 times, at which point the reaction was allowed to continue stirring under hydrogen at 50 psi at room temperature for one hour. The amine solution was filtered over Celite, and concentrated under reduced pressure. It was then coevaporated three times with dry CH2Cl2 (5 mL). A tan oil resulted and was placed under high vacuum, covered with foil for 30 minutes. Then, 5-nitrobenzofuran-2-carboxylic acid (0.394 g, 1.90 mmol) and PyBOP (0.999 g, 1.92 mmol) were suspended in dry CH2Cl2 (220 mL). The amine was then dissolved in dry CH2Cl2 (30 mL) and added to the suspension via a syringe through a septum. The reaction was allowed to stir for 10 minutes, at which point dry N,N-Diisopropylethylamine (0.75 mL, 4.29 mmol) was added to the suspension. The solution turned clear yellow. It was covered with foil and the solution was stirred under nitrogen, at room temperature for two days. The solution was vacuum filtered and the filtrate was washed with water (1×75 mL), 10% HCl (1×75 mL), saturated Sodium bicarbonate (1×75 mL), and brine (1×75 mL). The organic layer was dried over sodium sulfate, vacuum filtered, and concentrated under reduced pressure to yield a yellow solid. The residue was purified on a silica gel column using a 5-20% EtOAc/hexane solvent system to give the desired product 2-(4-benzyloxy-2-(5-nitrobenzofuran-2-carboxamido)phenyl)ethyl chloride as a yellow solid (0.173 g, 22% yield). Rf=0.22 (20% EtOAc/hexane) M.p. 109-113° C. IR (neat) 3370, 3088, 3032, 2945, 2858, 1690, 1531, 1337, 1270, 1168, 1101, 1025, 753, 610 1H-NMR (500 MHz, CDCl3) 8.67 (d, 2.0, 1H), 8.64 (s br, 1H), 8.39 (dd, 2.0, 9.0, 1H), 7.73 (s, 1H), 7.70 (d, 9.0, 1H), 7.65 (d, 2.5, 1H), 7.45 (d, 8.0, 2H), 7.40 (t, 8.0, 2H), 7.36 (t, 8.0, 1H), 7.19 (d, 8.5, 1H), 6.89 (dd, 2.5, 8.5, 1H), 5.10 (s, 2H), 3.83 (t, 6.5, 2H), 3.14 (t, 6.5, 2H). FAB-MS (NBA) 451 (M+H+, 11). Accurate mass for C24H19N2O5Cl+H: calcd. 451.1060; obs. 451.1050.

1. customwhile degassing under vacuum
2. customThe degas/hydrogen exposure cycle
3. stirringto continue stirring under hydrogen at 50 psi at room temperature for one hour
4. filtrationThe amine solution was filtered over Celite
5. concentrationconcentrated under reduced pressure
6. customA tan oil resulted
7. additionadded to the suspension via a syringe through a septum
8. additionwas added to the suspension
9. stirringthe solution was stirred under nitrogen, at room temperature for two days
10. filtrationfiltered
11. washthe filtrate was washed with water (1×75 mL), 10% HCl (1×75 mL), saturated Sodium bicarbonate (1×75 mL), and brine (1×75 mL)
12. dry with materialThe organic layer was dried over sodium sulfate, vacuum
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customto yield a yellow solid
16. customThe residue was purified on a silica gel column

ORD record

ord-f2d79237bee74f8eb929c232cb355fdd

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06660742B2