702
BRENA-VALLE ET AL.
J ¼ 9.6, 4.2), 3.37 (s, 3H), 3.29 (dd, HB, J ¼ 9.6, 7.2), 2.35 (ddd, 1H, J ¼ 7.2,
3.3, 0.3), 2.32 (ddd, 1H, J ¼ 7.2, 4.5 0.3), 2.27–2.13 (m, 1H). 13C-NMR
(CDCl3): 178.3, 76.0, 58.8, 53.6, 29.54, 22.9. MS m/z (%): 129 (Mþ, 15),
84 (100), 56 (24), 41 (46). EI-HRMS calcd for C6H12NO2 (Mþ1)þ 130.0868,
found 130.0866.
Introduction of the amino protecting group (General procedure). The
substrate was dissolved in CH3CN. Next, DMAP (0.1 eq.) was added, fol-
lowed by solid BOC2O (1.2 eq), added in small portions. The mixture in the
flask, stoppered with a glass valve that allowed the relief of pressure buildup
(CO2 generation), monitored by TLC, was stirred 24 h; upon reaction com-
pletion it was concentrated in vacuo at r.t. The residue was dissolved in ether
and worked up as described elswhere.25
(S)-1-(tert-Butoxycarbonyl)-5-methoxymethyl-pyrrolidin-2-one 4 Pre-
pared as described above dissolving compound 3 (6.11 g; 47.36 mmol)
in 50 ml CH3CN, adding DMAP (0.584 g) and BOC2O (12.44 g). Yield:
813 g (75%) of a yellow oil. [ꢁ]D ¼ꢁ 75.31ꢀ (c ¼ 1.04; CHCl3); lit.26
[ꢁ]D ¼ꢁ 58.8ꢀ (c ¼ 1.0; CHCl3).
IR (film, cmꢁ1): 2981, 1787, 1710, 1313, 1154, 1023. 1H-NMR
(CDCl3): 4.28–4.22 (m, 1H), 3.58 (dd, 1H, J ¼ 9.6, 4.8), 3.51 (dd, 1H,
J ¼ 9.6, 3.0), 3.35 (s, 3H), 2.69 (ddd, 1H, J ¼ 1.77, 10.2, 1.2), 2.37 (ddd,
1H, J ¼ 17.7, 10.2, 2.7), 2.18–2.05 (m, 1H), 2.04–1.93 (m, 1H), 1.54
(s, 9H). 13C-NMR (CDCl3): 174.6, 149.8, 82.6, 73.3, 59.1, 57.1, 31.8, 27.9,
21.1. MS m/z (%): 230 (Mþ1, 10), 184 (21), 156 (32), 130 (44), 84 (100),
57 (93).
(S)-5-tert-Butoxycarbonylamino-6-methoxy-hexan-2-one 5 In a dry
100 ml round bottom flask provided with stirring bar, septum and under
Argon atmosphere, pyrrolidone 4 (8 g; 34.93 mmol) was dissolved in 15 ml
anhydrous THF. The flask was cooled in a dry ice/acetone bath kept at
ꢁ60ꢀ to ꢁ40ꢀC and under stirring, an ethereal solution of 3M methyl mag-
nesium bromide (20 ml; 1.7 eq.) was added dropwise via syringe. The bath
was next removed and the resulting milky, slightly yellow mixture was
stirred 1 h at r.t., cooled to ꢁ20ꢀC and quenched with 30 ml of a NH4Cl
saturated aqueous solution. After phase separation, the aqueous was
extracted with ethyl ether (3Â30 ml), the extracts combined with the organic
phase and worked up as usual. The product was crystallized from an ethyl
ether-hexane mixture. Yield: 6.5 g (75.8%) of a slightly yellow crystalline
compound; m.p. 42ꢀC. [ꢁ]D ¼ꢁ 13.5ꢀ (c ¼ 1.0; CHCl3). IR (film, cmꢁ1):
1
2976, 1714, 1525, 1455, 1366, 1171. H-NMR (CDCl3): 4.75 (br. s. 1H),
3.7–3.66 (m, 1H), 3.36–3.33 (m, 2H), 3.33 (s, 3H), 2.52 (dt, 2H, J ¼ 7.3,
2.1), 2.14 (s, 3H), 1.86–1.71 (m, 2H), 1.44 (s, 9H). 13C-NMR (CDCl3):
208.2, 155.6, 79.1, 74.7, 58.9, 49.7, 40.3, 29.8, 28.3, 26.2. MS m/z
(%): 245 (Mþ, 23), 190 (49), 172 (21), 144 (71), 128 (34), 100 (95), 83 (44),