Sodium Nitrite → 4-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-amine

Temperature

0 °C

6-Iodo-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine [S12-5]. To solution of S12-4 (2.1 g, 12.8 mmol) in 50 mL of acetic acid cooled in ice bath was added NaNO2 (1.77 g, 26.9 mmol) slowly in portions. The resulting mixture was stirred at 0° C. for 10 min and was added KI (4.24 g, 38.4 mmol) in portions. The reaction mixture was stirred at 0° C. for 30 min, allowed to warm up to rt and stirred for 2 h. The resulting mixture was quenched with 100 mL of water, extracted with ethyl acetate (3×150 mL). The organic layer was combined, treated with Na2S2O3, washed with brine, dried over MgSO4 and purified by flash chromatography to give S12-5 (1.86 g, 53%) as a yellow solid. 1H NMR (CDCl3, 500 MHz) δ 6.64 (d, J=8.3 Hz, 1H), 6.56 (s, 1H), 6.48 (d, J=8.4 Hz, 1H), 4.25 (m, 2H), 3.24 (m, 2H), 2.85 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 138.1, 126.6, 120.5, 117.6, 111.9, 83.7, 64.8, 48.7, 36.5.

1. additionwas added KI (4.24 g, 38.4 mmol) in portions
2. stirringThe reaction mixture was stirred at 0° C. for 30 min
3. temperatureto warm up to rt
4. stirringstirred for 2 h
5. customThe resulting mixture was quenched with 100 mL of water
6. extractionextracted with ethyl acetate (3×150 mL)
7. additiontreated with Na2S2O3
8. washwashed with brine
9. dry with materialdried over MgSO4
10. custompurified by flash chromatography
11. customto give S12-5 (1.86 g, 53%) as a yellow solid

ORD record

ord-8d22183bef8244088ce4f2160d19a6e5

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328114B2