反应详情

温度

35 °C

tert-butyl 1-oxo-1-phenylethan-2-ylcarbamate (18) (1.4 g, 6.0 mmol, 1.0 equiv.) was added to a 100 mL RBF followed by EtOH (21 mL). Next, a 37% solution of formaldehyde (14.5 mL, 180 mmol, 30.0 equiv.) was added to the reaction mixture and the solution heated to 35° C. Finally, a 3.0 M solution of K2CO3 (410 mg, 3.0 mmol, 1.0 mL dH2O, 0.5 equiv.) was added to the reaction flask and the solution stirred vigorously for 30 min. The solution was neutralized with 1% HCl, transferred to a separatory funnel with a 2.3 M solution of NaCl (12.0 g, 205 mmol, 90.0 mL H2O), and extracted with CH2Cl2 (5×60 mL). The organic layers were combined and dried over Na2SO4. The resulting solution was concentrated on a rotary evaporator and dried under vacuum to give 2.9 g of crude oil. The residue was purified by flash column chromatography (4% MeOH/CH2Cl2) to give 720 mg (41%) of 1 as a white solid. Rf=0.20 (4% MeOH/CH2Cl2); mp=127-130° C.; IR (KBr) 3437, 3372, 2980, 2967, 1701, 1671, 1504, 1282, 1026 cm−1; 1H NMR (500 MHz, CDCl3) δ Major Rotamer: 8.03 (m, 2H, Ph-H), 7.43 (br s, 3H, Ph-H), 5.87 (br s, 1H, carbamate-NH), 5.35 (br s, 1H, Boc-NH—CH), 4.25 (d, J=11.0 Hz, 2H, CH—CH2), 4.02 (d, J=11.0 Hz, 2H, CH—CH2), 3.31 (br s, 2H, (CH2—OH2), 1.28 (s, 9H, t-butyl-CH3). Minor Rotamer: 8.19 (br s, 2H, Ph-H), 7.52 (br s, 3H, Ph-H), 1.07 (s, 9H, t-butyl-CH3); 13C NMR (125 MHz, CDCl3) δ 202.2, 201.1, 155.4, 154.9, 136.3, 135.1, 133.4, 132.7, 129.1, 128.7, 128.4, 82.2, 80.7, 68.2, 67.4, 64.6, 64.2, 28.2, 27.7; LRMS (ESI-MS m/z): Mass calcd for C15H21NO5 [M]+, 295.33. Found 296. Anal. calcd for C15H21NO5: C, 61.00; H, 7.17; N, 4.74 Found: C, 60.90; H, 7.17; N, 4.74.

1. extractionextracted with CH2Cl2 (5×60 mL)
2. dry with materialdried over Na2SO4
3. concentrationThe resulting solution was concentrated on a rotary evaporator
4. customdried under vacuum
5. customto give 2.9 g of crude oil
6. customThe residue was purified by flash column chromatography (4% MeOH/CH2Cl2)