3556
J. Perruchon et al.
PAPER
Sodium 3-[Acetyl(benzyloxy)amino]propane-1-sulfonate (5)
Acetamide 1 (1.0 g, 3 mmol, 1.0 equiv), Na2SO3 (567 mg, 4.5
mmol, 1.5 equiv), and H2O (20 mL) were added to a 50-mL two-
necked round-bottom flask flushed with inert gas and equipped with
a magnetic stirring bar. The heterogeneous mixture was heated to
reflux, and the reaction was monitored by TLC. After 18 h of stir-
ring, followed by evaporation of the solvent, the crude product was
dissolved in MeOH (3 mL) and filtered through a short pad of
Celite, which was thoroughly washed with MeOH. The solvent was
evaporated under reduced pressure.
13C{1H} NMR (100 MHz, CDCl3): d = 173.82 (CO), 49.13
(SO2CH2), 44.20 (NCH2), 29.70 (NCH3), 22.06 (COCH3), 20.84
(CH2).
Sodium 3-[Acetyl(hydroxy)amino]propane-1-sulfonate (9)
Sulfonate 5 (200 mg, 0.64 mmol, 1.0 equiv), pure MeOH (5 mL),
and, carefully, 10% Pd/C (45 mg, 0.06 mmol, 0.1 equiv) were added
to a 20-mL two-necked round-bottom flask flushed with inert gas
and equipped with a magnetic stirring bar. The heterogeneous mix-
ture was stirred at r.t. under H2, and the reaction was monitored by
TLC. After 3 h of stirring followed by evaporation of the solvent,
the crude product was dissolved in MeOH (3 mL) and filtered
through a short pad of Celite, which was thoroughly washed with
MeOH. The solvent was evaporated under reduced pressure; this
gave 9.
Yield: 900 mg (78%); white solid.
1H NMR (400 MHz, CDCl3): d = 7.34–7.31 (m, 5 H, CHar), 4.79 (s,
2 H, OCH2), 3.71 (t, 2 H, SO2CH2), 2.95 (t, 2 H, NCH2), 2.08 (s, 3
H, COCH3), 2.08 (m, 2 H, CH2).
13C{1H} NMR (100 MHz, CDCl3): d = 172.96 (CO), 134.21 (Cq),
129.41 (CH), 128.98 (CH), 129.26 (CH), 76.69 (OCH2), 47.29
(SO2CH2), 21.77 (CH2), 20.55 (COCH3).
Yield: 135 mg (95%); yellow oil.
1H NMR (400 MHz, CDCl3): d = 3.71 (t, 2 H, SO2CH2), 2.82 (t, 2
H, NCH2), 2.09 (s, 3 H, COCH3), 2.08 (m, 2 H, CH2).
3-[Acetyl(benzyloxy)amino]propane-1-sulfonyl Chloride (6)
Compound 5 (500 mg, 1.62 mmol), toluene (5 mL), and, dropwise,
SOCl2 (0.162 mL, 1 mL/0.1 mmol of acid) were added successively
to a 20-mL two-necked round-bottom flask flushed with inert gas
and equipped with a magnetic stirring bar. The mixture was heated
to reflux, and the reaction was monitored by TLC. After stirring of
the mixture for 2 h and evaporation of the solvent and excess SOCl2,
crude 6 was obtained; it was used without further purification in the
next step.
13C{1H} NMR (100 MHz, CDCl3): d = 174.10 (CO), 49.60
(SO2CH2), 44.65 (NCH2), 18.76 (COCH3), 17.53 (CH2).
N-(Benzyloxy)-N-[3-(methylsulfanyl)propyl]acetamide (10)
Acetamide 1 (500 mg, 1.5 mmol, 1.0 equiv) and THF (10 mL) were
added to a 25-mL two-necked round-bottom flask flushed with inert
gas and equipped with a magnetic stirring bar, and the mixture was
cooled to –78 °C. NaSMe (157 mg, 2.25 mmol, 1.5 equiv) and THF
(10 mL) were added to a second 50-mL two-necked round-bottom
flask flushed with inert gas and equipped with a magnetic stirring
bar, and the mixture was vigorously stirred for 15 min. The resulting
heterogeneous suspension was quickly added dropwise to the soln
of acetamide 1, and the mixture was stirred for 30 min at –78 °C and
allowed to stir at r.t. The reaction was monitored by TLC. After
completion of the reaction (1 h), the solvent was removed by evap-
oration and the crude product was purified by column chromatogra-
phy (silica gel, Et2O–pentane, 2:1).
N-(Benzyloxy)-N-[3-(methylsulfamoyl)propyl]acetamide (7)
Crude 6 (500 mg, 1.62 mmol, 1 equiv), MeNH2 (151 mg, 4.86
mmol, 3 equiv), and CH2Cl2 (20 mL) were added to a 20-mL two-
necked round-bottom flask flushed with inert gas and equipped with
a magnetic stirring bar. The resulting mixture was stirred at r.t., and
the reaction was monitored by TLC. After 12 h of stirring followed
by evaporation of the solvent and excess MeNH2, the crude product
was dissolved in Et2O (3 mL) and filtered through a short pad of
Celite, which was thoroughly washed with Et2O. Evaporation of the
solvent under reduced pressure afforded 7 in good chemical purity
without further purification.
Yield: 250 mg (65%); yellowish oil; Rf = 0.33 (Et2O–pentane, 2:1).
1H NMR (400 MHz, CDCl3): d = 7.40–7.37 (m, 5 H, CHar), 4.82 (s,
2 H, OCH2), 3.74 (t, 2 H, NCH2), 2.50 (t, 2 H, SCH2), 2.09 (s, 3 H,
SCH3), 2.08 (s, 3 H, COCH3), 1.93 (m, 2 H, CH2).
13C{1H} NMR (100 MHz, CDCl3): d = 172.55 (CO), 134.50 (Cq),
129.30 (CH), 129.04 (CH), 128.84 (CH), 76.45 (OCH2), 44.40
(NCH2), 31.53 (SCH2), 26.41 (CH2), 20.16 (SCH3), 15.49
(COCH3).
Yield: 80% (over two steps, from 5); pale yellow solid.
1H NMR (400 MHz, CDCl3): d = 7.40–7.37 (m, 5 H, CHar), 4.83 (s,
2 H, OCH2), 4.40 (d, 1 H, NH), 3.78 (t, 2 H, NCH2), 3.04 (t, 2 H,
SO2CH2), 2.76 (d, 3 H, NCH3), 2.10 (s, 3 H, COCH3), 2.09 (m, 2 H,
CH2).
13C{1H} NMR (100 MHz, CDCl3): d = 172.83 (CO), 134.24 (Cq),
129.39 (CH), 129.26 (CH), 128.91 (CH), 76.45 (OCH2), 48.83
(SO2CH2), 43.90 (NCH2), 29.41 (NCH3), 21.75 (COCH3), 20.54
(CH2).
N-(Benzyloxy)-N-[3-(methylsulfonyl)propyl]acetamide (11)
Acetamide 10 (250 mg, 0.99 mmol, 1.0 equiv), (NH4)2(Mo4O13)
(66.3 mg, 0.1 mmol), H2O2 (1 mL), and MeOH (7 mL) were added
to a 5-mL two-necked round-bottom flask equipped with a magnetic
stirring bar. The resulting heterogeneous mixture was stirred at r.t.
under N2 and the reaction was monitored by TLC. After completion
of the reaction (4 h), the solvent was removed by evaporation and
the crude product was purified by column chromatography (silica
gel, Et2O–pentane, 5:1).
N-Hydroxy-N-[3-(methylsulfamoyl)propyl]acetamide (8)
Acetamide 7 (200 mg, 0.66 mmol, 1.0 equiv), pure MeOH (5 mL),
and, carefully, 10% Pd/C (46 mg, 0.06 mmol, 0.1 equiv) were added
to a 20-mL two-necked round-bottom flask flushed with inert gas
and equipped with a magnetic stirring bar. The heterogeneous mix-
ture was stirred at r.t. under H2, and the reaction was monitored by
TLC. After 3 h of stirring followed by evaporation of the solvent,
the crude product was dissolved in MeOH (3 mL) and filtered
through a short pad of Celite, which was thoroughly washed with
MeOH. Evaporation of the solvent under reduced pressure gave
acetamide 8.
Yield: 284 mg (85%); white solid; Rf = 0.30 (Et2O–pentane, 5:1).
1H NMR (400 MHz, CDCl3): d = 7.40–7.37 (m, 5 H, CHar), 4.84 (s,
2 H, OCH2), 3.80 (t, 2 H, SO2CH2), 3.04 (t, 2 H, NCH2), 2.90 (s, 3
H, SO2CH3), 2.17 (m, 2 H, CH2), 2.11 (s, 3 H, COCH3).
13C{1H} NMR (100 MHz, CDCl3): d = 172.68 (CO), 133.90 (Cq),
129.32 (CH), 129.23 (CH), 128.84 (CH), 76.67 (OCH2), 52.08
(CH2SO2), 43.70 (NCH2), 40.72 (SO2CH3), 20.39 (CH2), 20.18
(COCH3).
Yield: 95%; yellow oil.
1H NMR (400 MHz, CDCl3): d = 3.73 (t, 2 H, NCH2), 3.06 (t, 2 H,
SO2CH2), 2.69 (s, 3 H, NCH3), 2.10 (s, 3 H, COCH3), 2.06 (m, 2 H,
CH2).
Synthesis 2007, No. 22, 3553–3557 © Thieme Stuttgart · New York