The Journal of Organic Chemistry
Article
3-Methyldihydro-2H-pyran-4(3H)-one (3(11)). The crude com-
pound was purified by method H (bp = 58−61 °C, 10 mmHg). 41.7 g
of the target product obtained as a colorless liquid in 73% yield.
1H NMR (400 MHz, Chloroform-d) δ 4.20 (m, 1H), 4.12 (ddd, J =
11.2, 6.4, 1.7 Hz, 1H), 3.67 (td, J = 11.5, 3.1 Hz, 1H), 3.28 (t, J = 10.8
Hz, 1H), 2.70−2.53 (m, 2H), 2.35 (dt, J = 14.2, 2.8 Hz, 1H), 0.95 (d,
J = 6.7 Hz, 3H). 13C{1H} NMR (126 MHz, Chloroform-d) δ 208.5,
74.1, 68.7, 46.1, 42.4, 9.8. EIMS, 70 eV, m/z (rel. int.): 114 [M]+
(46); 73 (100); 57 (11); 56 (40); 55 (15); 43 (15); 42 (56); 41 (22);
39 (14). Anal. Calcd for C6H10O2: C, 63.14; H, 8.83. Found: C,
62.76; H, 9.04.
tert-Butyl 3-Methyl-2,4-dioxopiperidine-1-carboxylate (3(17)).
The crude compound was purified by method G (system of solvents
MeCN/H2O). 53.4 g of the target product obtained as a white
powder in 47% yield (mp = 86−87 °C).
1H NMR (400 MHz, Chloroform-d) δ 4.55 (ddd, J = 14.4, 5.8, 2.3
Hz, 1H), 3.71 (ddd, J = 14.3, 12.1, 3.8 Hz, 1H), 3.56 (q, J = 6.6 Hz,
1H), 2.73−2.46 (m, 2H), 1.53 (s, 9H), 1.29 (d, J = 6.6 Hz, 3H).
13C{1H} NMR (126 MHz, Chloroform-d) δ 166.9, 166.3, 153.3,
102.3, 81.3, 42.2, 28.6, 28.3, 9.0. LCMS, negative mode, m/z: 227
[M]−; 226 [M − H]−. Anal. Calcd for C11H17NO4: C, 58.14; H, 7.54;
N, 6.16. Found: C, 58.52; H, 7.29; N, 6.12.
4-Methyldihydro-2H-pyran-3(4H)-one (3(12)). The crude com-
pound was purified by method H (bp = 67−68 °C, 10 mmHg). 44.5 g
of the target product obtained as a colorless liquid in 78% yield.
1H NMR (400 MHz, Acetonitrile-d3) δ 3.97−3.82 (m, 3H), 3.77
(td, J = 11.2, 3.3 Hz, 1H), 2.60 (m, 1H), 2.14 (m, 1H), 1.77−1.62 (m,
1H), 1.04 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (126 MHz,
Acetonitrile-d3) δ 209.4, 74.1, 65.9, 41.7, 34.0, 13.5. EIMS, 70 eV,
m/z (rel. int.): 114 [M]+ (65); 69 (17); 56 (100); 55 (20); 42 (14);
41 (63); 39 (21). Anal. Calcd for C6H10O2: C, 63.14; H, 8.83. Found:
C, 63.50; H, 8.72.
1,3-Dimethylpiperidin-4-one (3(18)). The crude compound was
purified by method F (system of solvents Hexane/MTBE). 31.2 g of
the target product obtained as a yellow oil in 49% yield.
1H NMR (400 MHz, Chloroform-d) δ 3.06−2.95 (m, 2H), 2.69−
2.52 (m, 2H), 2.39−2.23 (m, 5H), 2.02 (t, J = 11.2 Hz, 1H), 0.95 (d,
J = 6.7 Hz, 3H). 13C{1H} NMR (126 MHz, Chloroform-d) δ 210.5,
63.3, 56.2, 45.3, 44.2, 40.8, 11.9. EIMS, 70 eV, m/z (rel. int.): 128 [M
+ H]+ (5); 127 [M]+ (62); 84 (32); 71 (26); 70 (34); 57 (19); 56
(12); 55 (15); 44 (15); 43 (97); 42 (100); 41 (25); 39 (17). Anal.
Calcd for C7H13NO: C, 66.11; H, 10.30; N, 11.01. Found: C, 66.31;
H, 10.21; N, 11.23.
tert-Butyl 3-Methyl-4-oxopiperidine-1-carboxylate (3(13)). The
crude compound was purified by method F (system of solvents
Hexane). 89.6 g of the target product obtained as a white crystalline
solid in 84% yield (mp = 54−55 °C).
3-Methylpiperidine-2,4-dione (3(19)). The crude compound was
purified by method F (system of solvents MeCN/MeOH). 40.0 g of
the target product obtained as a white powder in 63% yield (mp =
125−126 °C).
1H NMR (400 MHz, Chloroform-d) δ 4.21−4.09 (m, 2H), 3.21
(ddd, J = 14.1, 10.3, 4.5 Hz, 1H), 2.80 (s, 1H), 2.57−2.31 (m, 3H),
1.45 (s, 9H), 1.00 (d, J = 6.6 Hz, 3H). 13C{1H} NMR (126 MHz,
Chloroform-d) δ 209.7, 154.5, 80.4, 49.8, 44.8, 43.8, 40.7, 28.4, 11.7.
EIMS, 70 eV, m/z (rel. int.): 213 [M]+ (2); 158 (17); 140 (14); 113
(14); 70 (11); 57 (100); 56 (25); 44 (11); 42 (14); 41 (34); 39 (13).
Anal. Calcd for C11H19NO3: C, 61.95; H, 8.98; N, 6.57. Found: C,
61.60; H, 8.93; N, 6.82.
1H NMR (400 MHz, DMSO-d6) δ 9.56 (s, 1H), 8.09 (s, 1H), 6.78
(s, 1H), 3.62 (q, J = 6.8 Hz, 1H), 3.54 (dddd, J = 12.9, 10.5, 4.5, 2.0
Hz, 1H), 3.26 (dtd, J = 13.5, 6.0, 2.6 Hz, 1H), 3.13 (td, J = 7.2, 2.5
Hz, 2H), 2.58−2.53 (m, 1H), 2.44−2.29 (m, 3H), 1.56 (s, 2H), 1.04
(d, J = 6.8 Hz, 3H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 207.1,
170.4, 170.2, 161.6, 101.1, 52.4, 37.9, 37.7, 35.5, 28.5, 8.7, 8.2. (keto-
enol tautomerism was observed) EIMS, 70 eV, m/z (rel. int.): 128 [M
+ H]+ (7); 127 [M]+ (100); 99 (45); 98 (15); 85 (24); 83 (14); 72
(15); 71 (10); 57 (31); 56 (84); 55 (31); 53 (11); 43 (14); 42 (16);
41 (10). Anal. Calcd for C6H9NO2: C, 56.68; H, 7.14; N, 11.02.
Found: C, 56.65; H, 7.20; N, 11.25.
tert-Butyl 3-Methyl-4-oxopyrrolidine-1-carboxylate (3(14)). The
crude compound was purified by method F (system of solvents
Hexane). 80.7 g of the target product obtained as a colorless viscous
oil in 81% yield.
1H NMR (400 MHz, Chloroform-d) δ 4.09 (s, 1H), 3.85 (s, 1H),
3.63 (d, J = 19.4 Hz, 1H), 3.13 (dd, J = 11.1, 9.1 Hz, 1H), 2.59 (d, J =
10.5 Hz, 1H), 1.45 (s, 9H), 1.14 (d, J = 7.1 Hz, 3H). 13C{1H} NMR
(126 MHz, Chloroform-d) δ 209.1, 154.3, 80.3, 52.6, 49.7, 42.4, 28.4,
12.6. EIMS, 70 eV, m/z (rel. int.): 199 [M]+ (3); 144 (12); 143 (12);
126 (14); 71 (13); 57 (100); 56 (28); 43 (12); 42 (35); 41 (60); 39
(24). Anal. Calcd for C10H17NO3: C, 60.28; H, 8.60; N, 7.03. Found:
C, 60.36; H, 8.47; N, 7.41.
(2R)-tert-Butyl 2-Methyl-3-oxo-8-azabicyclo[3.2.1]octane-8-car-
boxylate (3(20)). The crude compound was purified by method F
(system of solvents Hexane/MTBE). 6.22 g of the target product
obtained as a yellow oil in 52% yield.
1H NMR (400 MHz, Chloroform-d) δ 4.66−4.07 (m, 2H), 2.82−
2.33 (m, 2H), 2.33−2.12 (m, 1H), 2.11−1.88 (m, 2H), 1.68−1.51
(m, 2H), 1.46 (d, J = 4.7 Hz, 9H), 1.15 (d, J = 7.3 Hz, 2H), 0.99 (d, J
= 6.8 Hz, 1H). 13C{1H} NMR (126 MHz, Chloroform-d) δ 212.6,
208.4, 153.3, 79.9, 57.8, 53.1, 52.2, 46.4, 29.5, 28.4 (d, J = 4.0 Hz),
16.8. EIMS, 70 eV, m/z (rel. int.): 239 [M]+ (5); 166 (14); 124 (14);
82 (19); 69 (13); 68 (81); 67 (30); 57 (100); 56 (15); 55 (21); 41
(49); 39 (15). Anal. Calcd for C13H21NO3: C, 65.25; H, 8.85; N, 5.85.
Found: C, 65.41; H, 9.18; N, 5.50.
tert-Butyl 4-Methyl-3-oxopiperidine-1-carboxylate (3(15)). The
crude compound was purified by method F (system of solvents
Hexane). 75.7 g of the target product obtained as a colorless viscous
oil in 71% yield.
1H NMR (400 MHz, Chloroform-d) δ 4.05 (m, 1H), 3.86 (m,
2H), 3.35 (s, 1H), 2.42 (dp, J = 13.0, 6.6 Hz, 1H), 2.13−2.01 (m,
1H), 1.59 (qd, J = 12.1, 5.4 Hz, 1H), 1.42 (s, 9H), 1.09 (d, J = 6.7,
3H). 13C{1H} NMR (126 MHz, Chloroform-d) δ 207.9, 154.5, 80.4,
54.1, 42.5, 41.7, 30.8, 28.3, 14.1. EIMS, 70 eV, m/z (rel. int.): 213
[M]+ (13); 157 [M − t-Bu]+ (31); 140 (26); 129 (18); 128 (10); 114
[M − Boc + H]+ (10); 85 (14); 84 (27); 57 (100); 56 (32); 55 (14);
43 (61); 42 (53); 41 (82); 39 (43). Anal. Calcd for C11H19NO3: C,
61.95; H, 8.98; N, 6.57. Found: C, 62.18; H, 9.27; N, 6.97.
tert-Butyl 3,5-Dimethyl-4-oxopiperidine-1-carboxylate (3(16)).
The crude compound was purified by method F (system of solvents
Hexane). 70.5 g of the target product obtained as a white crystalline
solid in 62% yield (mp = 75−77 °C).
(3S,3aS,5aS,7S,9S,9aS,9bS)-3,5a,7,9-Tetramethyloctahydro-
naphtho[1,2-b]furan-2,8(3H,9bH)-dione (3(21)). The crude com-
pound was purified by method E (solvent Hexane). 0.13 g of the
target product obtained as a white powder in 96% yield (mp = 34−37
°C).
1H NMR (500 MHz, Chloroform-d) δ 3.79 (td, J = 10.6, 2.8 Hz,
1H), 2.78−2.64 (m, 1H), 2.40−2.29 (m, 1H), 2.31−2.20 (m, 1H),
2.22−2.14 (m, 1H), 1.92 (td, J = 10.3, 2.8 Hz, 1H), 1.87−1.78 (m,
1H), 1.73−1.67 (m, 1H), 1.67−1.32 (m, 4H), 1.33−1.15 (m, 7H),
1.03 (dd, J = 6.6, 2.7 Hz, 3H), 0.85 (d, J = 2.7 Hz, 2H). 13C{1H}
NMR (126 MHz, DMSO-d6) δ 217.7, 179.5, 83.9, 51.6, 49.4, 48.1,
45.9, 41.1, 40.1, 36.7, 35.7, 23.1, 21.2, 18.4, 16.0, 12.7. LCMS, positive
mode, m/z: 265 [M + H]+. Anal. Calcd for C16H24O3: C, 72.69; H,
9.15. Found: C, 72.59; H, 8.76.
1H NMR (400 MHz, Chloroform-d) δ 4.31 (s, 1H), 2.75−2.42 (m,
2H), 1.46 (s, 9H), 0.98 (d, J = 6.2 Hz, 6H). 13C{1H} NMR (126
MHz, Chloroform-d) δ 210.9, 154.4, 80.4, 51.2, 44.5, 28.4, 11.1.
EIMS, 70 eV, m/z (rel. int.): 227 [M]+ (3); 172 (23); 170 (13); 154
(12); 127 (31); 112 (11); 71 (16); 70 (18); 57 (100); 56 (28); 44
(17); 43 (14); 42 (27); 41 (45); 40 (15). Anal. Calcd for
C12H21NO3: C, 63.41; H, 9.31; N, 6.16. Found: C, 63.45; H, 9.23;
N, 6.09.
2,2-Dimethylpentan-3-one (3(22)). The crude compound was
purified by method H (34−37 °C, 20 mmHg). 39.4 g of the target
product obtained as a colorless liquid in 69% yield.
1H NMR (400 MHz, Chloroform-d) δ 2.47 (q, J = 7.2 Hz, 2H),
1.10 (s, 9H), 0.99 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (126 MHz,
Chloroform-d) δ 216.6, 44.0, 29.6, 26.5, 8.1. EIMS, 70 eV, m/z (rel.
7343
J. Org. Chem. 2021, 86, 7333−7346