506
P. K. Gadekar et al. / Tetrahedron Letters 55 (2014) 503–506
Table 4
S-MAc selectivity across other functional groups
Entrya
Substrate
Product
Yield (%)
70
O
O
HS
1a
1
S
7. Typical procedure for MAc protection: To a cooled (0 °C) solution of alcohol
(1.0 mmol) in anhydrous dichloromethane (5 ml), triethylamine (2.0 mmol),
methoxyacetyl chloride (1.5 mmol) and dimethylaminopyridine (0.1 mmol)
were added. The reaction mixture was stirred for 12–16 h at rt. The reaction
mass was diluted with water and extracted with dichloromethane. The organic
layer was washed with 1 N HCl, saturated sodium bicarbonate, brine and dried
over anhydrous sodium sulphate. The solvent was evaporated and purification
was carried out by flash column chromatography. Spectral data for the
representative examples: (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(2-
methoxyacetoxy)phenyl)propanoate (Table 3, entry 2): pale yellow solid; mp
65–67 °C; yield: 80%; 1H NMR (300 MHz, CDCl3): d 7.18–7.15 (d, J = 8.1 Hz, 2H),
7.08–7.06 (d, J = 8.1 Hz, 2H), 5.02–4.99 (m, 1H), 4.61–4.53 (m, 1H), 4.29 (s, 2H),
3.72 (s, 3H), 3.55 (s, 3H), 3.15–3.07 (m, 2H), 1.43 (s, 9H); 13C NMR (300 MHz,
DMSO-d6): d 172.99, 169.44, 155.86, 149.02, 135.78, 130.61(2C), 121.82(2C),
78.76, 69.33, 59.02, 55.53, 52.25, 36.16, 28.55 (3C); MS: m/z 391 [M+Na]+;
HRMS (ESI+) m/z [M+H]+ calcd for: C18H25NO7: 368.1704, found 368.1737;
HPLC: retention time 4.15 min, purity: 96.78%. (R)-Ethyl 2-(2-
methoxyacetamido)-3-((2-methoxyacetyl)thio) propanoate (Table 4, entry 6):
off white semi solid. Yield: 74%; 1H NMR (300 MHz, CDCl3): d 7.20 (s, 1H), 4.91–
4.85 (m, 1H), 4.27–4.20 (q, J = 6 Hz, 14.4 Hz, 2H), 4.10 (s, 2H), 3.98–3.93 (d,
J = 2.7 Hz, 2H), 3.53 (m, 1H), 3.49 (s, 3H), 3.44 (s, 3H), 1.34–1.29, 3.38–3.36 (m,
1H), (t, J = 6.9 Hz, 2H); 13C NMR (300 MHz, CDCl3) 199.01, 169.93, 169.77,
77.23, 71.63, 62.12, 60.04, 59.29, 51.18, 29.46, 14.07; MS: m/z 316.1 [M+Na]+;
HRMS (ESI+) m/z [M+H]+ calcd for C11H19NO6S: 294.1006, found 294.1002;
HPLC: retention time 4.5 min, purity: 95.38%.
8. Typical procedure for MAc deprotection: To a solution of protected alcohol
(1.0 mmol) in 4 ml of ethanol, sodium borohydride (0.5–2.0 equiv) was added
and stirred for 1–4 h at rt. The solvent was evaporated and ice-cold water was
added to the residual solid. The reaction mixture was extracted with ethyl
acetate, washed with brine and purified by flash column chromatography.
Spectral data for the representative examples. (S)-Methyl 2-((tert-
butoxycarbonyl)amino)-3-(4-hydroxyphenyl)propanoate (Table 3, entry 2a):
white solid; mp 105–107 °C; yield: 86%; 1H NMR (300 MHz, DMSO-d6): d 9.19
(s, 1H), 7.20–7.18 (d, J = 6.9 Hz, 1H), 6.99–6.97 (d, J = 7.5 Hz, 2H), 6.64–6.62 (d,
J = 7.8 Hz, 2H), 4.04–4.03 (m, 1H), 3.57 (s, 3H), 2.81–2.66 (m, 2H), 1.25 (s, 9H);
13C NMR (300 MHz, DMSO-d6): 73.23, 156.37, 155.85, 130.43(2C), 127.97,
115.42(2C), 78.68, 56.05, 52.14, 36.15, 28.58(3C); MS: m/z 318.1 [M+Na]+;
HPLC: retention time 3.32 min, purity: 99.85%. (R)-Ethyl 3-mercapto-2-(2-
methoxyacetamido)propanoate (Table 4, entry 6a): white solid; mp 109–
110 °C; yield: 74%; 1H NMR (300 MHz, CDCl3): d 7.30 (s, 1H), 4.9–4.8 (m, 1H),
4.31–4.23 (m, 2H), 4.02–3.90 (q, J = 4.8 Hz, 15.3 Hz, 2H), 3.47 (s, 3H), 3.12–3.29
(m, 2H), 1.34–1.29 (t, J = 7.2 Hz, 3H); 13C NMR (300 MHz, CDCl3): 170.14,
169.61, 71.75, 62.04, 59.30, 51.34, 34.91, 14.11; MS: m/z 220.2 [MÀH]+; HRMS
(ESI+) m/z [MÀH]+ calcd for C8H15NO4S; 220.0638 found 220.0633, HPLC:
retention time 13.53 min, purity: 90%.
1
O
O
2
3
79
76
S
S
HS
2a
2
HS
O
O
O
O
O
Cl
Cl
O
O
3
3a
H
N
H
N
O
4
5
73
79
O
O
O
S
S
HS
HS
4a
5a
4
O
O
OH
O
O
O
O
O
5
O
O
O
HS
O
S
O
NH
O
NH
6
7
74
72
O
6
6a
O
O
O
O
S
O
O
HS
O
O
HN
HN
O
O
7
7a
Reaction condition: ethanol, NaBH4 (1 equiv), rt, 1 h.8
a
Acknowledgment
We wish to thank John Proudfoot and Usha Patel for their
assistance in publishing this manuscript. We also wish to thank
the analytical facility at Piramal Enterprises Ltd.
References and notes