Pyridine → Propanedioic acid, 2-[2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)butylidene]-, 1,3-dimethyl ester

HRID 1427704Notes

Reaction equation

HRID 1427704 reaction equation
[CH3:1][CH:2]([CH2:5][CH2:6][C:7]1[C:12]([CH3:14])([CH3:13])[CH2:11][CH2:10][CH2:9][C:8]=1[CH3:15])[CH:3]=O.[C:16]([O:23][CH3:24])(=[O:22])[CH2:17][C:18]([O:20][CH3:21])=[O:19].N1C=CC=CC=1>ClC(Cl)(Cl)Cl.O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl>[CH3:1][CH:2]([CH2:5][CH2:6][C:7]1[C:12]([CH3:14])([CH3:13])[CH2:11][CH2:10][CH2:9][C:8]=1[CH3:15])[CH:3]=[C:17]([C:16]([O:23][CH3:24])=[O:22])[C:18]([O:20][CH3:21])=[O:19]

Participants

7

Reactant 3

HCID 1049PyridineHCID 7943Dimethyl malonateHCID 5791571-Cyclohexene-1-butanal, .alpha.,2,6,6-tetramethyl-

Product 1

HCID 24938928Propanedioic acid, 2-[2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)butylidene]-, 1,3-dimethyl esterYield 81%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Under water-free conditions titanium(IV) chloride(91 g, 0.5 mol) in tetrachloromethane (120 ml) are added dropwise within 45 min to tetrahydrofuran at 0° C. The mixture is stirred for another 30 min at this temperature, then 2-Methyl-4-(2,6,6-trimethylcyclohex-1-enyl)butanal 5 (50 g, 0.24 mol) (M. Malsui et al. Agric. Biol. Chem. 50, 1475-1480, 1986) and dimethyl malonate (31.7 g, 0.24 mot) in tetrahydrofuran (50 ml) are added within 15 min at 0° C. followed by dropwise addition of pyridine (76 g) in tetrahydrofuran (240 ml) over 90 min at 0° C. The orange-brown suspension is stirred for 18 h at 25° C. then poured upon ice/water and extracted with tert-butyl methyl ether. The combined organic layers are washed with water and conc. NaCl and dried over MgSO4. After filtration and evaporation of the solvents the crude product (75 g) is short-path-distilled giving 62.5 g 3a at 170° C./0.07 mbar (81% yield, purity>98%). Analytical data: 1H-NMR (400 MHz, CDCl3): δ0.95 (s, 6 H), 1.1 (d, 3 H), 1.4-1.5 (4H), 1.5-1.6 (2 H), 1.58 (s, 3 H), 1.8-2.0 (2 H), 2.5 (m, 1 H), 3.8 (s, 3 H), 3.85 (s, 3 H), 6.85 (d, 1 H) ppm. 13C-NMR (400 MHz, CDCl3): 19.45 (t), 19.55 (q), 19.75 (q), 26.4 (t), 28.5 (q), 32.7 (t), 34.8 (s), 35.7 (d), 36.8 (t), 39.7 (t), 52.1 (q), 32.2 (q), 126.7 (s), 127.1 (s), 136.8 (s), 154.9 (d), 164.4 (s), 166.0 (s), MS (El): m/z (%) 322 (M′, 10), 307 ([M-15]′, 2), 275 (6), 259 (7), 243 (16), 215 (11), 200 (18), 187 (19), 175 (20), 173 (16), 172 (100), 153 (22), 145 (28), 140 (70), 137 (27), 135 (34), 123 (60), 122 (28), 121 (42), 109 (35), 108 (34), 95 (62), 93 (36), 81 (44), 79 (33), 55 (36), 41 (35). IR (film): 2950 (m), 2926 (m), 2865 (m), 1725 (s), 1642 (w), 1454 (w), 1433 (m), 1363 (w), 1327 (w), 1246 (s), 1221 (s), 1204 (s), 1168 (w), 1104 (w), 1054 (m), 991 (w), 945 (w), 925 (w), 833 (w), 762 (w).

Workup

  1. stirringThe orange-brown suspension is stirred for 18 h at 25° C.
  2. extractionextracted with tert-butyl methyl ether
  3. washThe combined organic layers are washed with water and conc. NaCl
  4. dry with materialdried over MgSO4
  5. filtrationAfter filtration and evaporation of the solvents the crude product (75 g)
  6. distillationis short-path-distilled

Sources & evidence

ORD record
ord-42178e7227c64a338c819a21e6532bf9
Source dataset
uspto-grants-2015_01
Patent number
US08933253B2

Reaction notes

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