2
H, bs, CH CO), 2.70 (2/10 of 2H, bs, CH CO), 3.52 (5/10 of 1H, m, NH), 3.67-3.73 (6H, m,
2
2
OCH ), 3.79 (5/10 of 1H, m, NH), 3.91-4.03 (1H, m, NCHCH ), 4.28-4.38 (2H, m, POCH ), 4.85-
3
3
2
4
.91 (2H, s, OCH Ph), 6.78-6.80 (2H, m, CH ), 7.06-7.09 (2H, m, CH ), 7.33-7.36 (5H, m,
2
Ar
Ar
1
3
CHAr(Bn)), 9.24 (5/10 of 1H, bs, N(H)OBn), 9.37 (5/10 of 1H, bs, N(H)OBn); C NMR (125.8
MHz, CDCl ): δ 21.1 (NCHCH ), 35.2 (CH CO), 35.8 (CH CO), 50.3 (NCHCH ), 50.5 (NCHCH ),
3
C
3
2
2
3
3
5
1
1
2.8 (CO CH ), 55.8 (ArOCH ), 63.4 (POCH ), 63.6 (POCH ), 78.4 (OCH Ph), 78.5 (OCH Ph),
2
3
3
2
2
2
2
14.8 (CHAr(PMP)), 121.2-121.4 (CHAr(PMP)), 128.8-129.0 (CHAr(Bn)), 129.3-129.4 (CHAr(Bn)), 135.4-
3
35.7 (CAr(Bn)), 144.2 (C OP), 156.9 (C O CH ), 167.8 (CONH), 174.2 (d, J = 6.8 Hz,
Ar
Ar
3
C-P
3
31
CO CH ), 174.5 (d, J = 6.9 Hz, CO CH ); P NMR (162.0 MHz, CDCl ): δ 2.70, 3.00; MS
2
3
C-P
2
3
3
P
+
+
(
EI) : m/z calculated for C H N O PNa [M+Na] 489.14, found 489.14.
2
1 27 2 8
5
.1.12. N-(Benzyloxy)-3-hydroxy-N-methylpropanamide-3-[(4-methoxy)phenyl
(methoxyalaninyl) phosphoramidate] (16b)
To a solution of alcohol 14b (194 mg, 0.93 mmol), triethylamine (0.15 mL, 1.02 mmol), DMAP
57 mg, 0.47 mmol) in dry DCM (2.8 mL) was treated with a solution of compound 13 (860
(
mg, 2.8 mmol) in DCM (2.2 mL) at -40 °C. The resulting mixture was warmed up to room
temperature and stirred overnight. A saturated aqueous solution of NH Cl (10 mL) was
4
added and the aqueous layer was extracted with DCM (2 x 15 mL). The organic layers were
collected, dried over anhydrous Na SO , filtered and solvents were removed under reduced
2
4
pressure. The crude product was purified by flash chromatography (EtOAc/cyclohexane, 9:1)
to give 16b as a colorless oil (213 mg, 48 %) and as a mixture of two diastereomers in a 50:50
1
ratio. Rf = 0.23 (EtOAc/petroleum ether, 6:4). H NMR (400 MHz, CDCl ): δ 1.35 (5/10 of 3H,
3
3
3
d, J = 7.0 Hz, NCHCH ), 1.39 (5/10 of 3H, d, J = 7.1 Hz, NCHCH ), 2.66-2.88 (2H, m, CH CO),
3
3
2
3
.19 (5/10 of 3H, s, NCH ), 3.20 (5/10 of 3H, s, NCH ), 3.70-3.72 (3H, m, OCH ), 3.75 (3H, m,
3
3
3
OCH ), 4.00-4.08 (1H, m, NCHCH ), 4.31-4.48 (2H, m, POCH ), 4.76-4.81 (2H, m, OCH Ph),
3
3
2
2
1
3
6
.79-6.81 (2H, m, CH ), 7.09-7.014 (2H, m, CH ), 7.34-7.39 (5H, m, CH
); C NMR (125.8
Ar
Ar
Ar(Bn)
MHz, CDCl ): δ 21.3 (NCHCH ), 33.2 (CH CO), 33.6 (NCH ), 50.3 (NCHCH ), 50.4 (NCHCH ),
3
C
3
2
3
3
3
5
2.6 (CO CH ), 55.8 (ArOCH ), 62.9 (POCH ), 76.6 (OCH Ph), 114.7 (CHAr(PMP)), 121.4-121.5
2
3
3
2
2
(CHAr(PMP)), 128.9 (CHAr(Bn)), 129.3 (CHAr(Bn)), 129.5 (CHAr(Bn)), 134.4 (CAr(Bn)), 144.5-144.6
4
3
(
C OP), 156.6 (C O CH ), 171.8 (d, J = 9.4 Hz, CONCH ), 174.2 (d, J = 7.4 Hz, CO CH ),
Ar
Ar
3
C-P
3
C-P
2
3
2
2