Isobutyraldehyde → HCID 56948846, compound

HRID 333937Notes

Reaction equation

HRID 333937 reaction equation
[Cl-].[Li+].C(OP(C[C:12]([CH:14]1[CH2:19][CH2:18][N:17]([C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH3:30])[CH:21]=2)[CH2:16][CH2:15]1)=[O:13])(OCC)=O)C.[CH:31](N(C(C)C)CC)(C)C.[CH:40](=O)[CH:41]([CH3:43])[CH3:42].[Cl-].[NH4+]>C(#N)C.ClCCl.O>[CH3:42][CH:41]([CH3:43])/[CH:40]=[CH:31]/[C:12]([CH:14]1[CH2:15][CH2:16][N:17]([C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH3:30])[CH:21]=2)[CH2:18][CH2:19]1)=[O:13]

Participants

9

Reactant 5

HCID 6561IsobutyraldehydeHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 86691592HCID 86691592, compound

Product 1

HCID 56948846HCID 56948846, compoundYield 29.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Lithiumchloride (4.2 mg, 0.1 mmol) which had been dried before in vacuum at 125° C. was placed in anhydrous acetonitrile (4 ml), the mixture was cooled to −78° C. and diethoxyphosphoryl-1-[1-(2-methyl-4-quinolyl)-4-piperidyl]ethanone from step B (40 mg, 0.1 mmol) dissolved in 1 ml anhydrous acetonitrile was added dropwise with stirring. The mixture was allowed to reach room temperature, stirring was continued for 10 minutes and diisopropylethylamine (10.1 mg, 0.1 mmol) and isobutyraldehyde (7.2 mg, 0.1 mmol) were added. Stirring was continued overnight. Water and dichloromethane (10 ml each) were added and the mixture poured into saturated ammoniumchloride solution (20 ml). The phases were separated, the aqueous phase extracted with dichloromethane (3×) and the combined organic phases washed with brine, dried over sodium sulfate and the solvent removed under reduced pressure. The raw product was purified with preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile). 9.5 mg of an amber-coloured solid were obtained (0.029 mmol, 29%).

Workup

  1. additionwas added dropwise
  2. customto reach room temperature
  3. stirringstirring
  4. stirringStirring
  5. waitwas continued overnight
  6. customThe phases were separated
  7. extractionthe aqueous phase extracted with dichloromethane (3×)
  8. washthe combined organic phases washed with brine
  9. dry with materialdried over sodium sulfate
  10. customthe solvent removed under reduced pressure
  11. customThe raw product was purified with preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

Sources & evidence

ORD record
ord-cd9d767e5c5c4d9ba66559d7bb3f81fc
Source dataset
uspto-grants-2014_11
Patent number
US08883791B2

Reaction notes

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