Isobutyl iodide → HCID 59327423, compound

HRID 1879923Notes

Reaction equation

HRID 1879923 reaction equation
CCN(C(C)C)C(C)C.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].I[CH2:29][CH:30]([CH3:32])[CH3:31]>C1COCC1.CCCCCC>[CH2:26]([O:25][C:23]([C:20]1([CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:21][CH2:22][N:17]([C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])[CH2:18][CH2:19]1)=[O:24])[CH3:27]

Participants

6

Reactant 3

HCID 10556Isobutyl iodideHCID 81531DiisopropylethylamineHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

Product 1

HCID 59327423HCID 59327423, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-5 °C

Procedure

4.7 g (47 mmol) DIPEA in THF at −5° C. was treated slowly with 29.1 mL (47 mmol) n-Buli (1.6N in hexane) and stirred for 30 min at −5° C. and subsequently cooled to −75° C. and stirred for 2 h. A solution of 10 g (39 mmol) ethyl 1-tert-butoxycarbonylpiperidine-4-carboxylate (commercially available) in THF was added and the mixture was stirred for 2 h at −75° C. 8.51 g (47 mmol) 1-iodo-2-methylpropane was added and the mixture was allowed to stir to room temperature over night. The mixture was quenched at 0° C. with citric acid 10% aq. and extracted with ethyl acetate. The combined organic layers were washed with NaCl aq. sat., dried with Na2SO4, filtered and evaporated. The residue was purified by column chromatography on silica eluting with a gradient formed heptane and t-butyl-methylether. The combined product fractions were evaporated to yield 10.2 g (84%) of the title compound as light yellow oil. MS (m/e): 331.2 (M+NH4+).

Workup

  1. temperaturesubsequently cooled to −75° C.
  2. stirringstirred for 2 h
  3. stirringthe mixture was stirred for 2 h at −75° C
  4. stirringto stir to room temperature over night
  5. customThe mixture was quenched at 0° C. with citric acid 10% aq.
  6. extractionextracted with ethyl acetate
  7. washThe combined organic layers were washed with NaCl aq. sat.
  8. dry with materialdried with Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by column chromatography on silica eluting with a gradient
  12. customformed heptane and t-butyl-methylether
  13. customThe combined product fractions were evaporated

Sources & evidence

ORD record
ord-4aaa46bf10a240dfa0843b0981be0379
Source dataset
uspto-grants-2012_11
Patent number
US08318749B2

Reaction notes

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