Aluminum(III) Chloride → 1,4-Diethyl-1,2,3,4-tetrahydropyrido[3,4-b]pyrazine

HRID 1670652Notes

Reaction equation

HRID 1670652 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[H-].[H-].[H-].[H-].[Li+].[Al+3].[C:11]([N:14]1[CH2:19][CH2:18][N:17]([C:20](=O)[CH3:21])[C:16]2[CH:23]=[CH:24][N:25]=[CH:26][C:15]1=2)(=O)[CH3:12]>CC(OC)(C)C>[CH2:20]([N:17]1[CH2:18][CH2:19][N:14]([CH2:11][CH3:12])[C:15]2[CH:26]=[N:25][CH:24]=[CH:23][C:16]1=2)[CH3:21]

Participants

5

Reactant 3

HCID 6451240Aluminum(III) ChlorideHCID 21226445Aluminium lithium hydrideHCID 597630781-(4-Acetyl-3,4-dihydro-2H-pyrido[3,4-b]pyrazin-1-yl)ethanone

Product 1

HCID 574357831,4-Diethyl-1,2,3,4-tetrahydropyrido[3,4-b]pyrazine

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

1.56 g (11.69 mmol) of AlCl3 were suspended in 60 ml of MTBE at room temperature. After stirring for 45 minutes, the reaction mixture was cooled to 0° C. and LiAlH4 (1.32 g, 34.65 mmol) was added a little at a time. After the addition was complete and the mixture had been stirred for another 15 minutes, compound 8 (1.00 g, 4.56 mmol) was added and the mixture was stirred at 0° C. for another hour. The reaction mixture was subsequently refluxed for 8 hours and after cooling to room temperature was poured into ice water. The precipitated inorganic solid was filtered off with suction and washed twice with 30 ml of DCM. The aqueous phase was brought to a pH of 12 and extracted three times with 40 ml of DCM. The combined extracts were dried over Na2SO4 and the solvent was distilled off on a rotary evaporator. The crude product was purified by flash chromatography on silica gel (EtOAc/MeOH/NEt3, 10:0.5:1). This gave 0.52 g (60%) of a colorless oil which solidified in the freezer. Rf=0.47 (EtOAc/MeOH/NEt3, 10:0.5:1). 1H NMR: (400 MHz, CDCl3): δ=1.15 (q, 3J=14 Hz, 6H, CH3), 3.22 (m, 3J=6 Hz, 2H, H-3), 3.23 (m, 2J=14 Hz, 4H, CH2), 3.42 (m, 3J=6 Hz, 2H, H-2), 6.34 (d, 3J=5.2 Hz, 1H, H-8), 7.69 (s, 1H, H-5), 7.75 (d, 3J=5.2 Hz, 1H, H-7). 13C NMR: (100 MHz, CDCl3): δ=10.1, 10.4 (CH3), 44.6, 46.5 (CH2, C-2, C-3), 44.9, 45.0 (CH2), 104.0 (C-8), 130.5, 130.1 (Cq), 131.8 (C-5), 140.7 (C-7). GC-MS (EI): RT 8.63 min, m/e (%): 192 (10), 191 (M+, 100), 190 (4), 177 (8), 176 (95), 175 (5), 162 (11), 161 (8), 160 (5), 148 (13), 147 (10), 146 (8), 135 (2), 134 (9), 133 (6), 131 (8), 121 (2), 119 (4), 118 (3), 107 (3), 104 (2), 92 (2), 91 (2), 80 (8), 77 (4) IR (KBr): ν=3436 (s), 3112 (w), 3019 (w), 2964 (w), 1661 (s), 1686 (vs), 1583 (m), 1497 (m), 1409 (s), 1363 (w), 1332 (m), 1311 (s), 1260 (m), 1249 (w), 1232 (m), 1220 (m), 1180 (m), 1150 (w), 1119 (m), 1064 (w), 1035 (m), 985 (m), 970 (m), 886 (s), 858 (m), 847 (m), 802 (m), 765 (w), 740 (w), 704 (w), 647 (w), 614 (w), 592 (w), 577 (m), 570 (m), 507 (w) cm−1. HRMS (EI) calculated for C11H17N3 [M+]: 191.1422; found: 191.1430.

Workup

  1. additionAfter the addition
  2. stirringthe mixture had been stirred for another 15 minutes
  3. stirringthe mixture was stirred at 0° C. for another hour
  4. temperatureThe reaction mixture was subsequently refluxed for 8 hours
  5. temperatureafter cooling to room temperature
  6. filtrationThe precipitated inorganic solid was filtered off with suction
  7. washwashed twice with 30 ml of DCM
  8. extractionextracted three times with 40 ml of DCM
  9. dry with materialThe combined extracts were dried over Na2SO4
  10. distillationthe solvent was distilled off on a rotary evaporator
  11. customThe crude product was purified by flash chromatography on silica gel (EtOAc/MeOH/NEt3, 10:0.5:1)
  12. customRT 8.63 min, m/e (%)

Sources & evidence

ORD record
ord-b5a5bc820ca941ec915aa354e83a28b0
Source dataset
uspto-grants-2011_08
Patent number
US07994169B2

Reaction notes

Loading…