2,2,6,6-Tetramethylpiperidine → HCID 57456307, compound

HRID 1992413Notes

Reaction equation

HRID 1992413 reaction equation
[Li]CCCC.CC1(C)CCCC(C)(C)N1.[Cl:16][C:17]1[CH:22]=[N:21][CH:20]=[CH:19][N:18]=1.[CH2:23]([O:30][C:31]1[CH:32]=[C:33]([CH:36]=[CH:37][CH:38]=1)[CH:34]=[O:35])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CCOC(C)=O.C1COCC1>[Cl:16][C:17]1[C:22]([CH:34]([C:33]2[CH:36]=[CH:37][CH:38]=[C:31]([O:30][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:32]=2)[OH:35])=[N:21][CH:20]=[CH:19][N:18]=1

Participants

7

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 73277ChloropyrazineHCID 743423-BenzyloxybenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 57456307HCID 57456307, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

A THF (20 mL) solution of 2M n-BuLi in cyclohexanes was cooled to −78° C. and charged with 2,2,6,6-tetramethylpiperidine (1.8 mL, 10.48 mmol). The reaction vessel was removed from the cooling bath and allowed to warm to 0° C. for 15 min, then cooled back to −78° C. and charged with 2-chloropyrazine (1.0 g, 8.73 mmol) dropwise. The reaction was allowed to react for 15 min, and charged with a 10.0 mL THF solution of 3-benzyloxybenzaldehyde (2.0 g, 9.60 mmol) slowly at −78° C. The reaction was allowed to react for 2 h (TLC analysis (30% EtOAc:Hex)) and quenched with HClconc. (2.0 mL), and H2O (30.0 mL). The crude product was extracted from the aqueous/THF layer 4× with CH2Cl2. The organic layers were combined and washed 1× with H2O, 1×brine, dried over Na2SO4 and concentrated in vacuo, to yield the crude product as a brown oil. High performance flash chromatography (HPFC) with a 70 g Jones silica gel column (30% EtOAc:Hex) was applied to yield the desired product as a pale yellow solid; 1H NMR (CDCl3, 400 MHz) δ 5.01 (s, 3H), 6.00 (s, 2H), 6.90-6.96 (m, 3H), 7.23-7.41 (m, 6H), 8.36 (d, 1H, J=2.4 Hz), 8.54 (d, 1H, J=2.5 Hz); MS (ES) 327.16 (M+1), 329.16 (M+3).

Workup

  1. customThe reaction vessel was removed from the cooling bath
  2. temperaturecooled back to −78° C.
  3. customto react for 15 min
  4. customquenched with HClconc
  5. extractionThe crude product was extracted from the aqueous/THF layer 4× with CH2Cl2
  6. washwashed 1× with H2O, 1×brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customto yield the crude product as a brown oil

Sources & evidence

ORD record
ord-0d8cf589689f4e37ba04f1892fb6d944
Source dataset
uspto-grants-2010_01
Patent number
US07648987B2

Reaction notes

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