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HETEROCYCLES, Vol. 79, 2009
4.90 cm3, 35.1 mmol) in MeCN (60 cm3) was added in one portion. After 5 h the solution was filtered
through a pad of celite and evaporated in vacuo. The residue was taken up in EtOAc (300 cm3), triturated
for 30 min and again filtered through a pad of celite. The filtrate was extracted with HCl (2 M, 3 × 300 cm3),
cm3), the aqueous extracts were basified to pH 11 with conc. aq. NH3 solution (35%) and back-extracted
with CH2Cl2 (3 × 100 cm3). The organic extracts were combined, dried (anhydrous MgSO4), filtered and
evaporated in vacuo. Purification by column chromatography with CH2Cl2-MeOH (9 : 1) as eluent afforded
afforded 3-[(2E)-2-{2-[methoxy(methyl)amino]-2-oxoethylidene}pyrrolidin-1-yl]propyl acetate (22) as a
light yellow oil (7.73 g, 85%); Rf (EtOAc–MeOH 4 : 1) 0.81; vmax (film)/cm−1 2939 (C-H, m), 1734 (ester
C=O, s), 1646 (amide C=O, s), 1426 (m), 1367 (m) 1233 (s), 1042 (s), 998 (m); δH (300 MHz; CDCl3) 5.10
5.10 (1H, s, C=CH), 4.11 (2H, t, J = 6.3 Hz, CH2OAc), 3.67 (3H, s, OMe), 3.36 and 3.31 (4H, 2 ×
overlapping t, J = 7.1 Hz, J = 7.3 Hz, ring and chain CH2N), 3.21 (2H, t, J = 7.7 Hz, CH2C=), 3.15 (3H, s,
NMe), 2.07 (3H, s, OCOMe), 1.94 (4H, coincident quintets, J = 6.8 Hz, remaining CH2); δC (75 MHz;
CDCl3) 171.8, 170.8, 164.3, 76.7, 61.9, 60.8, 52.4, 43.1, 33.0, 32.6 , 25.4, 21.2, 20.8; m/z (EI) 270 (M+, 1%),
1%), 211 (13), 210 (100), 168 (13), 148 (12), 74 (22). HRMS (EI) Found: M+, 270.1562. C13H22N2O4
requires 270.1580.
(2E)-2-[1-(3-Hydroxypropyl)pyrrolidin-2-ylidene]-N-methoxy-N-methylethanamide (23)
3-[(2E)-2-{2-[Methoxy(methyl)amino]-2-oxoethylidene}pyrrolidinyl]propyl acetate (22) (7.73 g, 28.6
mmol) and K2CO3 (7.91 g, 57.2 mmol) were stirred in MeOH (100 cm3) for 3 h. The mixture was filtered
through celite. The filtrate was evaporate in vacuo, and then taken up in CHCl3 (300 cm3) and washed with
a saturated sodium chloride solution (300 cm3). The aqueous phases were back extracted with CHCl3 (3 ×
250 cm3), dried (anhydrous MgSO4), filtered and evaporated in vacuo to afford the crude product.
Purification by column chromatography with CH2Cl2-MeOH (9
:
1) as eluent gave
(2E)-2-[1-(3-hydroxypropyl)pyrrolidin-2-ylidene]-N-methoxy-N-methylethanamide (23) (5.45 g, 83%) as
a yellow oil; Rf 0.85 (CH2Cl2-MeOH 7 : 3); vmax (film)/cm−1 3353 (O-H, v br, m), 2938 and 2874 (C-H, m)
1646 (s), 1613 (s), 1438 (m), 1423 (m), 1360 (m), 1170 (m), 1055 (m), 918 (m), 828 (m), 810 (m), 720 (m),
660 (m); δH (300 MHz; CDCl3) 5.14 (1H, s, C=CH), 3.68 and 3.67 (5H, overlapping t and s, J = 6.0 Hz,
CH2OH and OMe), 3.38 and 3.36 (4H, 2 × overlapping t, J = 7.0 Hz, 6.9 Hz, ring and chain CH2N), 3.22
(2H, t, J = 7.8 Hz, CH2C=), 3.14 (3H, s, NMe), 2.04 (1H, s, OH), 1.93 (2H, quintet, J = 7.1 Hz, chain
CH2CH2CH2), 1.84 (2H, quintet, J = 6.6 Hz, ring 4-H); δC (75 MHz; CDCl3) 172.1, 164.8, 76.3, 60.9, 59.9,
52.4, 42.9, 33.1, 32.7, 29.1, 21.2; m/z (EI) 228 (M+, 2%), 169 (12), 168 (100), 150 (5), 120 (5) 110 (5), 108
(5). HRMS (EI) Found, M+, 228.1467. C11H20N2O3 requires 228.1474.
N-Methoxy-N-methyl-1,2,3,5,6,7-hexahydroindolizine-8-carboxamide (24)