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PAPER
matography (silica gel, hexane–EtOAc, 3:1) to yield 74 mg (70%)
J = 7.7 Hz, 1 H, 5¢-HB), 3.83 (d, J = 13.3 Hz, 1 H, NCH2Ph), 3.97
(mc, 1 H, 5¢-HA), 3.90 (d, J = 6.5 Hz, 1 H, 2-H), 4.69 (td, J = 6.5, 7.7
Hz, 1 H, 4¢-H), 6.17 (d, J = 2.2 Hz, 1 H, 4-H), 7.21–7.38 (m, 5 H,
C6H5), 7.50 (d, J = 2.2 Hz, 1 H, 5-H).
13C NMR (CDCl3, 125 MHz): d = 25.4, 26.6 (2 q, CH3), 38.5 (q,
NCH3), 59.2 (t, NCH2Ph), 61.9 (d, C-2), 67.6 (t, C-5¢), 75.5 (d, C-
4¢), 105.1 (d, C-4), 109.7 (s, C-2¢), 127.0, 128.2, 129.2, 138.9 (3 d,
s, C6H5), 135.6 (d, C-5), 174.4 (s, C-3).
of ketone 12 as a colorless oil; [a]D22 +5.2 (c 1.0, CHCl3).
IR (film): 3445 (O–H), 3090–3030 (=C–H), 2985–2875 (C–H),
1725 (C=O), 1250 cm–1 (C–O).
1H NMR (CDCl3, 500 MHz): d = 1.40, 1.45 (2 s, 3 H each, CH3),
2.39 (s, 3 H, NCH3), 3.13 (dd, J = 4.4, 8.5 Hz, 1 H, 4-H), 3.33 (s, 3
H, OCH3), 3.70 (t, J = 7.7 Hz, 1 H, 5¢-HB), 3.74–3.83 (m, 3 H, 1-H,
3-H), 4.02 (dd, J = 6.0, 7.7 Hz, 1 H, 5¢-HA), 4.32 (d, J = 19.3 Hz, 1
H, NCH2Ph), 4.45 (d, J = 19.3 Hz, 1 H, NCH2Ph), 4.63 (ddd,
J = 6.0, 7.7, 8.5 Hz, 1 H, 4¢-H), 7.15–7.33 (m, 5 H, C6H5).
MS (EI, 80 eV, 110 °C): m/z (%) = 301 (M+, <1), 200 (M+
–
C5H9O2, 91), 91 (CH2Ph+, 100).
13C NMR (CDCl3, 125 MHz): d = 25.7, 26.8 (2 q, CH3), 38.3 (q,
NCH3), 60.1 (q, OCH3), 62.1 (t, C-1), 66.9 (d, C-4), 67.4 (t, C-5¢),
67.5 (t, NCH2Ph), 73.6 (d, C-4¢), 88.3 (d, C-3), 109.3 (s, C-2¢),
126.8, 128.1, 128.8, 139.6 (3 d, s, C6H5), 210.9 (s, C=O).
HRMS: m/z [M+] calcd for C17H23N3O2: 301.17902; found:
301.17854.
Anal. Calcd for C17H23N3O2 (301.4): C, 67.75, H, 7.69; N, 13.94.
Found: C, 67.08; H, 7.22; N, 13.01.
MS (EI, 80 eV, 100 °C): m/z (%) = 337 (M+, <1), 236 (M+ –
+
C5H9O2, 28), 101 (C5H9O2 , 16), 91 (CH2Ph+, 100).
(2S,3R)-3-(Benzylmethylamino)-3-(2H-pyrazol-3-yl)propane-
1,2-diol (24)
HRMS: m/z [M+ – CH3] calcd for C18H27NO5: 322.16516; found:
322.16654.
Pyrazole derivative syn-19 (440 mg, 1.46 mmol) was dissolved in
AcOH (90%, 10 mL) and stirred under reflux for 2 h. AcOH was re-
moved under reduced pressure and the residue was recrystallized
from hexane–EtOAc to give the pure product 24 (342 mg, 90%) as
colorless crystals; mp 153–155 °C; [a]D22 –6.0 (c 0.4, CHCl3).
IR (KBr): 3325 (O–H), 3085–3030 (=C–H), 2985–2865 cm–1 (C–
H).
1H NMR (CD3OD, 500 MHz): d = 2.10 (s, 3 H, CH3), 3.28 (dd,
J = 4.7, 11.7 Hz, 1 H, 1-HB), 3.35 (d, J = 12.5 Hz, 1 H, NCH2Ph),
3.56 (dd, J = 5.9, 11.7 Hz, 1 H, 1-HA), 3.65 (d, J = 12.5 Hz, 1 H,
NCH2Ph), 3.95 (d, J = 8.9 Hz, 1 H, 3-H), 4.06 (mc, 1 H, 2-H), 6.30
(s, 1 H, 5-H), 7.22–7.35 (m, 5 H, C6H5), 7.65 (s, 1 H, 6-H).
(2S,3S,4R,4¢S)-4-(Benzylmethylamino)-2-(tert-butyldimethyl-
siloxy)-4-(2¢,2¢-dimethyl-1,3-dioxolan-4¢-yl)-3-methoxybutyr-
aldehyde (15)
1,2-Oxazine 14 (100 mg, 0.230 mmol) was treated with MeOTf
(0.23 mL, 0.230 mmol) as described in GP1. The mixture was
stirred at r.t. for 6 h. Then it was cooled to 0 °C, treated with Et3N
(93 mL, 0.690 mmol), and stirred at this temperature for 1 h. After
workup, the crude product (108 mg) was purified by column chro-
matography (silica gel, hexane–EtOAc, 2:1) to yield 64 mg (62%)
of aldehyde 15 as a colorless oil; [a]D22 +24.6 (c 0.8, CHCl3).
IR (film): 3090–3030 (=C–H), 2985–2855 (C–H), 1730 (C=O),
1255 cm–1 (C–O).
13C NMR (CD3OD, 125 MHz): d = 37.8 (q, NCH3), 59.7 (t,
NCH2Ph), 62.4 (d, C-3), 64.4 (t, C-1), 71.2 (d, C-2), 105.1 (d, C-5),
128.0, 129.2, 130.2, 139.6 (3 d, s, C6H5), 135.6 (s, C-4); the signal
for C-6 could not be detected.
1H NMR (CDCl3, 500 MHz): d = 0.06, 0.14 [2 s, 3 H each,
Si(CH3)2], 0.90 [s, 9 H, C(CH3)3], 1.39, 1.43 (2 s, 3 H each, CH3),
2.20 (s, 3 H, NCH3), 2.99 (dd, J = 2.7, 8.9 Hz, 1 H, 4-H), 3.35 (dd,
J = 2.7, 5.1 Hz, 1 H, 3-H), 3.43 (s, 3 H, OCH3), 3.59 (t, J = 7.9 Hz,
1 H, 5¢-HB), 3.73 (d, J = 12.8 Hz, 1 H, NCH2Ph), 3.99 (d, J = 12.8
Hz, 1 H, NCH2Ph), 4.04 (dd, J = 5.9, 7.9 Hz, 1 H, 5¢-HA), 4.12 (dd,
J = 5.1, 7.5 Hz, 1 H, 2-H), 4.61 (ddd, J = 5.9, 7.9, 8.9 Hz, 1 H, 4¢-
H), 7.19–7.30 (m, 5 H, C6H5), 9.55 (d, J = 7.5 Hz, 1 H, CHO).
MS (FAB): m/z (%) = 289 (M+ + Na, 23), 262 (M+ + H, 46), 200
(M+ – C2H5O2, 35), 91 (CH2Ph+, 100).
HRMS: m/z [M+ – C2H5O2] calcd for 200.11765; found: 200.11877.
Anal. Calcd for C14H19N3O2 (261.3): C, 64.35; H, 7.33; N, 16.08.
Found: C, 63.78; H, 7.05; N, 15.72.
13C NMR (CDCl3, 125 MHz): d = –5.3, –4.5 [2 q, Si(CH3)2], 18.2,
25.8 [s, q, C(CH3)3], 25.7, 26.8 (2 q, CH3), 38.2 (q, NCH3), 58.9 (q,
OCH3), 59.0 (t, NCH2Ph), 63.0 (d, C-4), 68.0 (t, C-5¢), 73.2 (d, C-
2), 73.9 (d, C-4¢), 89.5 (d, C-3), 108.9 (s, C-2¢), 126.8, 127.9, 128.6,
138.7 (3 d, s, C6H5), 196.6 (d, CHO).
2-[(4¢S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-3-methoxy-1-methyl-
1H-pyrrole (29)
A suspension of Raney-Ni in H2O (ca. 67 mg) was washed with
MeOH (3 × 5 mL). Then, anhyd MeOH (3 mL) was added and the
solution was saturated with H2 for 1 h. Then a solution of aldehyde
syn-2a (30 mg, 0.095 mmol) in anhyd MeOH (2 mL) was added and
the mixture was stirred for 1 h under H2 atmosphere at normal pres-
sure at r.t. Filtration through a pad of Celite and removal of the sol-
vent in vacuo afforded 23 mg of pyrrole 29. The product was
purified by column chromatography (silica gel, hexane–EtOAc,
MS (EI, 80 eV, 70 °C): m/z (%) = 451 (M+, <1), 350 (M+ – C5H9O2,
38), 91 (CH2Ph+, 100).
HRMS: m/z [M+ – C5H9O2] calcd for C24H41NO5Si: 350.21515;
found: 350.21475.
22
(2R,4¢S)-Benzyl-[(2¢,2¢-dimethyl-1,3-dioxolan-4¢-yl)(2H-pyra-
zol-3-yl)methyl]methylamine (syn-19)
6:1) to yield 14 mg (70%) as a colorless oil; [a]D –8.0 (c 0.45,
CHCl3).
Aldehyde syn-2a (250 mg, 0.780 mmol) and hydrazine hydrate
(0.40 mL, 9.50 mmol) were mixed in anhyd EtOH (6 mL). TFA (58
mL, 0.780 mmol) was added and the mixture was stirred under re-
flux for 2 h. EtOH was removed in vacuo and H2O (5 mL) was add-
ed to the residue, which was extracted with CH2Cl2 (3 × 10 mL).
The combined CH2Cl2 layers were dried (Na2SO4) and concentrated
to yield 243 mg (quant) of pyrazole derivative syn-19 as colorless
crystals; mp 68–70 °C; [a]D22 –30.7 (c 1.7, CHCl3).
IR (film): 2985–2850 (C–H), 1620 cm–1 (C=C).
1H NMR (CDCl3, 500 MHz): d = 1.42, 1.50 (2 s, 3 H each, CH3),
3.63 (s, 3 H, NCH3), 3.72 (s, 3 H, OCH3), 4.11 (dd, J = 6.9, 8.2 Hz,
1 H, 5¢-HB), 4.21 (t, J = 8.2 Hz, 1 H, 5¢-HA), 5.27 (dd, J = 6.9, 8.2
Hz, 1 H, 4¢-H), 5.81 (d, J = 3.0 Hz, 1 H, 4-H), 6.40 (d, J = 3.0 Hz, 1
H, 5-H).
13C NMR (CDCl3, 125 MHz): d = 25.3, 26.5 (2 q, CH3), 35.3 (q,
NCH3), 58.6 (q, OCH3), 66.6 (t, C-5¢), 69.1 (d, C-4¢), 94.6 (d, C-4),
108.6 (s, C-2¢), 110.8 (s, C-2), 120.7 (d, C-5), 147.4 (s, C-3).
IR (KBr): 3260 (N–H), 3085–3030 (=C–H), 2985–2800 (C–H),
1675 cm–1 (C=C).
1H NMR (CDCl3, 500 MHz): d = 1.40, 1.42 (2 s, 3 H each, CH3),
2.23 (s, 3 H, NCH3), 3.47 (d, J = 13.3 Hz, 1 H, NCH2Ph), 3.58 (t,
MS (EI, 80 eV, 30 °C): m/z (%) = 211 (M+, 74), 140 (100).
Synthesis 2011, No. 1, 109–118 © Thieme Stuttgart · New York