Diisopropylethylamine → {1-[(1S,9aR)-1-(Octahydro-quinolizin-1-yl)methyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 2267715Notes

Reaction equation

HRID 2267715 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)C(C)C)C.[CH2:24]1[CH2:33][C@H:32]2[N:27]([CH2:28][CH2:29][CH2:30][C@H:31]2[CH2:34]O)[CH2:26][CH2:25]1.[I-].C(C[P+](C)(C)C)#N>C(#N)CC>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:34][C@H:31]2[C@@H:32]3[N:27]([CH2:26][CH2:25][CH2:24][CH2:33]3)[CH2:28][CH2:29][CH2:30]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 91461(-)-LUPININEHCID 7238334-(N-Boc-amino)piperidineHCID 10514344(Cyanomethyl)trimethylphosphanium iodide

Product 1

HCID 59600141{1-[(1S,9aR)-1-(Octahydro-quinolizin-1-yl)methyl]-piperidin-4-yl}-carbamic acid tert-butyl esterYield 108.1%

Reagents, catalysts & solvents 1

HCID 7854PropionitrileSolvent

Conditions

Temperature
120 °C

Procedure

3 (3 g, 15 mmol) is dissolved in 150 ml of propionitril. Ethyldiisopropylamine (10.2 ml, 60 mmol), (−)-lupinine (2.5 g, 15 mmol) and cyanomethyl-trimethyl-phosphonium iodide (Zaragoza reagent, 7.3 g, 30 mmol) are added. The reaction mixture is heated to 120° C. and stirred for 22 hours. Then the mixture is evaporated under reduced pressure. The residue is dissolved with ethyl acetate, washed 10% K2CO3- and NaCl-solution, and dried over Na2SO4. Evaporation gave 5.7 g of a brown oil. The crude product is purified by Flash-chromatography (ethyl acetate, then methanol/ethyl acetate (4:6), silicagel).

Workup

  1. customThen the mixture is evaporated under reduced pressure
  2. dissolutionThe residue is dissolved with ethyl acetate
  3. washwashed 10% K2CO3- and NaCl-solution
  4. dry with materialdried over Na2SO4
  5. customEvaporation

Sources & evidence

ORD record
ord-e325455780b5466481c3f46951f24da6
Source dataset
uspto-grants-2010_12
Patent number
US07858781B2

Reaction notes

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