Sodium Hydroxide → 4'-((2-Butyl-4-oxo-1,3-diazaspiro(4.4)non-1-ene-3-yl)methyl)(1,1'-biphenyl)-2-carbonitrile

HRID 1275808

Reaktionsgleichung

Reaktionsgleichung von HRID 1275808
Cl.[CH2:2]([CH:6]1[NH:10][C:9](=[O:11])[C:8]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[NH:7]1)[CH2:3][CH2:4][CH3:5].[OH-].[Na+].Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[C:27]([C:32]#[N:33])=[CH:28][CH:29]=[CH:30][CH:31]=2)=[CH:22][CH:21]=1>[Cl-].C[N+](CCCC)(CCCC)CCCC.C(Cl)Cl>[CH2:2]([C:6]1[N:10]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]3[C:27]([C:32]#[N:33])=[CH:28][CH:29]=[CH:30][CH:31]=3)=[CH:24][CH:25]=2)[C:9](=[O:11])[C:8]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[N:7]=1)[CH2:3][CH2:4][CH3:5]

Komponenten

6

Edukt 3

HCID 14798Sodium HydroxideHCID 15019124'-(Bromomethyl)-2-cyanobiphenylHCID 221178832-Butyl-1,3-diazaspiro[4.4]nonan-4-one hydrochloride

Produkt 1

HCID 98431164'-((2-Butyl-4-oxo-1,3-diazaspiro(4.4)non-1-ene-3-yl)methyl)(1,1'-biphenyl)-2-carbonitrileAusbeute 82,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 91822Tributylmethylammonium chlorideKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A mixture of 28.9 g (125 mmoles) of 2-butyl-1,3-diazaspiro[4.4]nonan-4-one, hydrochloride, 1.3 mL of 75% aqueous solution of methyl tributylammonium chloride, 90 mL (10 N) of 33% aqueous sodium hydroxide and 90 mL of methylene chloride was vigorously stirred for 5 minutes at room temperature and then cooled to 7-12° C. To this vigorously stirred cooled mixture at 7-12° C. was added a solution of 36.04 g (132 mmoles, amount determined quantitatively by HPLC) in 300 mL of methylene chloride of 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile over a period of 70 minutes. After that, the reaction mixture was allowed to warm up to room temperature and stirred additionally at room temperature for a half hour. Then the phases were separated and the organic phase was washed twice with 90 mL of water. The organic phase was concentrated under reduced pressure to the minimum agitation volume, and methyl tertiarybutyl ether was added. Concentration was continued to displace the dichloromethane, and the product was crystallized from the methyl tertiarybutyl ether solution. The crystals were collected on a filter, washed with cold 120 ml of methyl-tertiarybutyl ether and dried in a vacuum oven at 40° C. and a pressure of 3.1 mm Hg to give 39.9 g (82.4%) of the title compound having a laboratory HPLC of HI 99.8.

Aufarbeitung

  1. temperaturecooled to 7-12° C
  2. stirringTo this vigorously stirred
  3. temperaturecooled mixture at 7-12° C.
  4. additionwas added a solution of 36.04 g (132 mmoles, amount
  5. customof 70 minutes
  6. temperatureto warm up to room temperature
  7. stirringstirred additionally at room temperature for a half hour
  8. customThen the phases were separated
  9. washthe organic phase was washed twice with 90 mL of water
  10. concentrationThe organic phase was concentrated under reduced pressure to the minimum agitation volume, and methyl tertiarybutyl ether
  11. additionwas added
  12. concentrationConcentration
  13. customthe product was crystallized from the methyl tertiarybutyl ether solution
  14. customThe crystals were collected on a filter
  15. washwashed with cold 120 ml of methyl-tertiarybutyl ether
  16. customdried in a vacuum oven at 40° C.

Quellen und Nachweise

ORD-Eintrag
ord-47c2ef1f13df43dbae2e64a7c196773e
Quelldatensatz
uspto-grants-2000_12
Patentnummer
US06162922

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