Diisopropylamine → HCID 68243888, compound

HRID 588409Notes

Reaction equation

HRID 588409 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.[CH:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21]>C1COCC1>[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1[CH:20]([OH:21])[CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 122873-ChloropyridineHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 68243888HCID 68243888, compoundYield 73.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Diisopropylamine (1.82 mL, 12.9 mmol) was dissolved in THF (40 mL) and cooled to −78° C. nBuLi (4.93 mL, 2.5 M in hexanes, 12.3 mmol) was added drop-wise and the solution was warmed to room temperature, stirred for 45 min and re-cooled −78° C. A solution of 3-chloropyridine (1.40 g, 12.3 mmol) in THF (6 mL) was added and the reaction mixture was stirred at −78° C. for 4 h. A solution of tert-butyl 4-formylpiperidine-1-carboxylate (2.89 g, 13.6 mmol) in THF (6 mL) was added and the reaction mixture was warmed to r.t. and stirred for 2 h. The reaction mixture was quenched with water (60 mL) and extracted with DCM (100 mL and 2×30 mL). The combined organic fractions were dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography to give the title compound (2.94 g, 73%) as a yellow gum. LCMS (ES+): 271.0 (M+H-tBu)+.

Workup

  1. additionwas added drop-wise
  2. temperaturere-cooled −78° C
  3. stirringthe reaction mixture was stirred at −78° C. for 4 h
  4. temperaturethe reaction mixture was warmed to r.t.
  5. stirringstirred for 2 h
  6. customThe reaction mixture was quenched with water (60 mL)
  7. extractionextracted with DCM (100 mL and 2×30 mL)
  8. dry with materialThe combined organic fractions were dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by normal phase column chromatography

Sources & evidence

ORD record
ord-822c2d6ccec3462691c94724962cdf74
Source dataset
uspto-grants-2016_01
Patent number
US09227967B2

Reaction notes

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