Diisopropylamine → HCID 86585362, compound

HRID 1954641Notes

Reaction equation

HRID 1954641 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.CCCCCC.[CH2:19]([O:21][C:22]([C:24]1([C@@H:27]2[CH2:31][N:30]([C@H:32]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH3:33])[C:29](=[O:40])[C@H:28]2[F:41])[CH2:26][CH2:25]1)=[O:23])[CH3:20].C(C1C=CC=C(C(C)(C)C)C=1O)(C)(C)C.[Cl-].[NH4+]>O1CCCC1>[CH2:19]([O:21][C:22]([C:24]1([C@H:27]2[CH2:31][N:30]([C@H:32]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH3:33])[C:29](=[O:40])[C@H:28]2[F:41])[CH2:26][CH2:1][CH2:25]1)=[O:23])[CH3:20]

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 25517Ammonium ChlorideHCID 314052,6-Di-tert-butylphenolHCID 86585363HCID 86585363, compoundHCID 178418339Butyllithium

Product 1

HCID 86585362HCID 86585362, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

Under a nitrogen atmosphere, diisopropylamine (2.97 ml, 21.19 mmol) was dissolved in dry tetrahydrofuran (30 ml). After cooling the solution to -78° C., a 1.63 M solution of n-butyllithium in n-hexane (10.8 ml, 17.60 mmol) was added dropwise thereinto over a period of 5 minutes. Then, the liquid reaction mixture was stirred at 0° C. for 15 minutes and cooled to -78° C. Next, a solution (30 ml) of trans 4-(1-ethoxycarbonyl-cyclopropyl)-3-fluoro-1-[1-(S)-phenylethyl]-2-pyrrolidone (optical isomer B; 4.71 g, 14.13 mmol) in dry tetrahydrofuran was added dropwise thereinto over a period of 5 minutes. The liquid reaction mixture was stirred at -78° C. for 3 minutes. Then, it was added dropwise into a solution (40 ml) of 2,6-di-tert-butylphenol (4.37 g, 21.18 mmol) in dry tetrahydrofuran over a period of 5 minutes. The liquid reaction mixture was stirred at -78° C. for 10 minutes and a saturated aqueous solution of ammonium chloride (200 ml) was added thereto. Next, the liquid reaction mixture was brought back to room temperature and the organic layer was taken up. The aqueous layer was extracted with chloroform (100 ml×2). The combined organic layer was washed with water (100 ml×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 1.96 g (42%) of the starting compound (eluent:n-hexane:ethyl acetate=2:1) and 1.79 g (38%) of the title compound (eluent:n-hexane:ethyl acetate=3:2) each as an oily substance.

Workup

  1. customThen, the liquid reaction mixture
  2. temperaturecooled to -78° C
  3. waitover a period of 5 minutes
  4. customThe liquid reaction mixture
  5. stirringwas stirred at -78° C. for 3 minutes
  6. customThe liquid reaction mixture
  7. stirringwas stirred at -78° C. for 10 minutes
  8. customNext, the liquid reaction mixture
  9. customwas brought back to room temperature
  10. extractionThe aqueous layer was extracted with chloroform (100 ml×2)
  11. washThe combined organic layer was washed with water (100 ml×2)
  12. dry with materialdried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-70f2ca4f620b470faa5cf69475bfb63f
Source dataset
uspto-grants-2000_09
Patent number
US06121285

Reaction notes

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