Benzyl Alcohol → Benzyl carbamate

Temperature

70 °C

To a mixture of 27 (5.32 g, 11.2 mmol, 1 equiv), triethylamine (6.24 mL, 44.8 mmol, 4.0 equiv), and crushed, activated 4 Å molecular sieves (~20 g) in toluene (53 mL) was added diphenylphosphoryl azide (3.10 mL, 14.4 mmol, 1.2 equiv), and the resulting suspension was heated to 70° C. for 2 h. The reaction mixture was cooled to 23° C., and benzyl alcohol (1.73 mL, 16.8 mmol, 1.5 equiv) was then added. The suspension was stirred at 23° C. for 1 h, filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography (gradient elution: 20→50% ethyl acetate in hexanes) to afford 3 (5.90 g, 93%) as a pale yellow solid (mp 102°-103° C.). Rf 0.25 (33% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3) d 7.40 (m, 1H, Ph-H & ArCH), 6.92 (s, 1H, ArH), 6.70 (s (br), 1H, NH), 5.99 (s, 2H, ArOCH2OAr), 5.10 (s, 2H, Cbz CH2), 4.70 (m (br), 2H, Bn CH2), 4.58 (t (br), 1H, J=unres, CH(OCH3)2), 4.23 (d (br), 2H, J=unres, CO2 CH2CH), 3.39 (s, 6H, OCH3), 2.18 (s, 3H, ArCH3), Z configuration verified by 5.8% NOE of Ar-H upon irradiation of N--H; 13C NMR (100 MHz, CDCl3) d 165.0, 151.7, 148.1, 143.4, 136.3, 135.9, 128.6, 128.5, 128.4, 128.3, 128.1, 126.3, 123.6, 120.1, 113.9, 105.0, 101.5, 101.1, 67.3, 64.0, 53.9, 9.4; IR (neat film) 3350 (w, br), 2940 (w), 1718 (s), 1498 (m), 1473 (m), 1423 (m), 1247 (s), 1193 (s), 1130 (m), 1094 (s), 1069 (m) cm-1 ; HRMS (FAB+) m/z: calcd for C30H31NO9Na (MNa+) 572.1896, found 572.1909.

1. customcrushed
2. temperatureThe reaction mixture was cooled to 23° C.
3. filtrationfiltered
4. concentrationthe filtrate was concentrated
5. customThe residue was purified by flash column chromatography (gradient elution: 20→50% ethyl acetate in hexanes)

ORD record

ord-fd34adc9631743af885a1be00fa10ac6

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05721362