Lithium Hexamethyldisilazide → 1-(6-Methoxypyridin-2-yl)-2,2-dipyridin-3-ylethanamine

HRID 1360122Notes

Reaction equation

HRID 1360122 reaction equation
[Li+].C[Si]([N-:6][Si](C)(C)C)(C)C.[CH3:11][O:12][C:13]1[N:18]=[C:17]([CH:19]=O)[CH:16]=[CH:15][CH:14]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[CH:22]=1>C1COCC1>[CH3:11][O:12][C:13]1[N:18]=[C:17]([CH:19]([NH2:6])[CH:27]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[C:23]2[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=2)[CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 123253926-Methoxy-2-pyridinecarboxaldehydeHCID 147626403,3'-Methylenedipyridine

Product 1

HCID 574257591-(6-Methoxypyridin-2-yl)-2,2-dipyridin-3-ylethanamineYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

LiHMDS (2.45 mL, 1.2 M in THF, 2.94 mmole) was added to a flame-dried round bottom flask. The mixture was cooled to 0° C. then 6-methoxypyridine-2-carbaldehyde (Comins, Daniel L.; Killpack, Michael O. J. Org. Chem. 1990, 55, 69-73, 161 mg, 1.18 mmole) was added. After 30 minutes di-3-pyridylmethane (200 mg, 1.18 mmole) in dry THF (2.0 mL) was added. After 2 hr the mixture was warmed to RT, quenched with saturated NH4Cl, and extracted with CH2Cl2(3×) and iBuOH (2×). The combined organic layers were dried (MgSO4), filtered, and concentrated. The residue was taken up in MeOH (5 mL) and H2NOH (0.4 mL, 50% in H2O) was added. After 18 hr the mixture was concentrated. Flash column (gradient, 0-10% MeOH/CH2Cl2) gave 1-(6-methoxypyridin-2-yl)-2,2-dipyridin-3-ylethanamine as a pale yellow oil (168 mg, 47%): 1H-NMR (500 MHz, CDCl3) δ 8.64 (d, J=1.95 Hz, 1H), 8.51 (dd, J=1.46 and 3.17 Hz, 1H), 8.36 (d, J=1.95 Hz, 1H), 8.32 (dd, J=1.46 and 3.18 Hz, 1H), 7.76 (d, J=7.82 Hz, 1H), 7.49 (d, J=8.06 Hz, 1H), 7.37-7.27 (m, 2H), 7.09 (m, 1H), 6.56 (d, J=7.08 Hz, 1H), 6.52 (d, J=7.81 Hz, 1H), 4.59 (d, J=9.28 Hz, 1H), 4.42 (d, J=9.28 Hz, 1H), 3.91 (s, 3H).

Workup

  1. temperatureAfter 2 hr the mixture was warmed to RT
  2. customquenched with saturated NH4Cl
  3. extractionextracted with CH2Cl2(3×) and iBuOH (2×)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionH2NOH (0.4 mL, 50% in H2O) was added
  8. concentrationAfter 18 hr the mixture was concentrated

Sources & evidence

ORD record
ord-083ec73da97a4683aed56762f76c2eac
Source dataset
uspto-grants-2011_02
Patent number
US07879839B2

Reaction notes

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