反应详情

Under positive argon pressure, an orange suspension of tert-butyl ethyl(2-(7-(thiophene-2-carboximidamido)-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl)carbamate (4 g, 9.29 mmol) in MeOH (30 mL) and 1N HCl (30 mL) was refluxed for 1 hour. The mixture was then cooled to room temperature, transferred to an ice bath, and 1N NaOH (75 mL) was then added. The solution turned a milky green colour with a black suspension. The mixture was then treated with CH2Cl2 (50 mL) and stirred for half an hour. After this time, the mixture was transferred to a separatory funnel and the product was extracted into CH2Cl2 (2×50 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was subjected to flash chromatography on silica gel using the following sequence of eluents: EtOAc; 1:99 (2M NH3 in MeOH):CH2Cl2; 2.5:97.5 (2M NH3 in MeOH):CH2Cl2; and 5:95 (2M NH3 in MeOH):CH2Cl2. A brown solid was obtained (2 g, 65.1%). 1H-NMR (CDCl3) δ 7.40-7.37 (m, 2H), 7.07-7.04 (m, 1H), 6.75-6.72 (m, 1H), 6.52-6.50 (m, 2H), 4.82 (brs, 2H), 4.24 (t, J=4.5 Hz, 2H), 3.39-3.31 (m, 4H), 2.86 (t, J=6.3 Hz, 2H), 2.71 (q, J=6.9 Hz, 2H), 1.13 (t, J=7.2 Hz, 3H); ESI-MS (m/z, %): 331 (MH+, 100), 260 (95); HPLC purity: 94.1% by area.

1. temperaturewas refluxed for 1 hour
2. customtransferred to an ice bath
3. customAfter this time, the mixture was transferred to a separatory funnel
4. extractionthe product was extracted into CH2Cl2 (2×50 mL)
5. dry with materialThe combined organic layers were dried (Na2SO4)
6. concentrationconcentrated
7. customA brown solid was obtained (2 g, 65.1%)