2,2,6,6-Tetramethylpiperidine → HCID 68814650, compound

HRID 732343

Reaction equation

HRID 732343 reaction equation
C([Li])CCC.CC1(C)CCCC(C)(C)N1.[C:16]([O:20][C:21]([N:23]1[CH:27]=[CH:26][CH:25]=[CH:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].[CH3:28][C:29]1[CH:56]=[CH:55][CH:54]=[CH:53][C:30]=1[CH2:31][N:32]([CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1[CH3:52])[C@@H:33]([CH2:36][C:37]1[CH:42]=[C:41]([F:43])[CH:40]=[C:39]([F:44])[CH:38]=1)[CH:34]=[O:35]>O1CCCC1>[C:16]([O:20][C:21]([N:23]1[CH:27]=[CH:26][CH:25]=[C:24]1[C@@H:34]([OH:35])[C@@H:33]([N:32]([CH2:31][C:30]1[CH:53]=[CH:54][CH:55]=[CH:56][C:29]=1[CH3:28])[CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1[CH3:52])[CH2:36][C:37]1[CH:42]=[C:41]([F:43])[CH:40]=[C:39]([F:44])[CH:38]=1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

6

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 643494tert-butyl 1H-pyrrole-1-carboxylateHCID 86614992HCID 86614992, compoundHCID 178418339Butyllithium

Product 1

HCID 68814650HCID 68814650, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-10 °C

Procedure

Add n-butyllithium (3.30 mL, 8.25 mmol, 2.5 M in hexanes) to a solution of 2,2,6,6-tetramethylpiperidine (1.40 mL, 8.18 mmol) in tetrahydrofuran (THF) (30 mL) at −78° C. over 2 min. Stir 5 min, then warm to −10° C. and stir 5 min, then cool to −78° C. Add N-tert-butoxycarbonylpyrrole (1.37 mL, 8.25 mmol) in THF (1.6 mL) over 3 min. Stir 30 min and add 2-(S)-[bis-(2-methylbenzyl)-amino]-3-(3,5-difluorophenyl)-propionaldehyde (2.96 g, 7.44 mmol) in THF (15 mL) over 5 min. Stir 60 min at −78° C., warm to 0° C. and stir 60 min. Cool −78° C. and quench with saturated aqueous ammonium chloride solution. Extract with ethyl acetate, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and dichloromethane) to give the title compound as a foam (0.416 g, 10%).

Workup

  1. stirringstir 5 min
  2. temperaturecool to −78° C
  3. stirringStir 30 min
  4. stirringStir 60 min at −78° C.
  5. temperaturewarm to 0° C.
  6. stirringstir 60 min
  7. temperatureCool −78° C.
  8. customquench with saturated aqueous ammonium chloride solution
  9. extractionExtract with ethyl acetate
  10. dry with materialdry (magnesium sulfate)
  11. concentrationconcentrate
  12. custompurify
  13. wash(silica gel chromatography, eluting with hexanes and dichloromethane)

Sources & evidence

ORD record
ord-8e478015b76044cc98413c62c33f9d85
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Linked notes

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