tert-Butanol → N-benzyloxycarbonyl-5-aminomethyl-4-(4-pyridyl)-3-(4-fluorophenyl)pyrazole

HRID 1167566Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1167566
[CH3:1][C:2]([O-])([CH3:4])[CH3:3].[K+].[CH3:7][C:8](O)([CH3:10])C.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[NH:23][N:22]=[C:21](N3CCN(C(OC(C)(C)C)=O)CC3)[C:20]=2[C:37]2[CH:42]=[CH:41][N:40]=[CH:39][CH:38]=2)=[CH:15][CH:14]=1.C(O[C:51]([NH:53]CC(C1CC(=O)N(O)C1=O)=O)=O)C1C=CC=CC=1.[OH2:65].NN.C1[CH2:72][O:71]CC1>O.C(OCC)(=O)C.CC(O)=O>[CH2:1]([O:65][C:72]([N:22]1[C:21]([CH2:51][NH2:53])=[C:20]([C:37]2[CH:38]=[CH:39][N:40]=[CH:41][CH:42]=2)[C:19]([C:16]2[CH:15]=[CH:14][C:13]([F:12])=[CH:18][CH:17]=2)=[N:23]1)=[O:71])[C:2]1[CH:4]=[CH:10][CH:8]=[CH:7][CH:3]=1

Komponenten

10

Edukt 6

HCID 6386tert-ButanolHCID 8028Tetrahydrofuran3×HCID 24654Hydrazine hydrate (1:1)HCID 22037183N-benzyloxycarbonyl-glycyl-N-hydroxysuccinimideHCID 220373211,1-dimethylethyl 4-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1-piperazinecarboxylateHCID 23665647Potassium tert-butoxide

Produkt 1

HCID 69409299N-benzyloxycarbonyl-5-aminomethyl-4-(4-pyridyl)-3-(4-fluorophenyl)pyrazole

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A 3 L round bottom flask fitted with a mechanical stirrer, N2 inlet and an addition funnel was was charged wtih 557 mL (0.56 mol) of 1 M t-BuOK in THF and 53 mL (0.56 mol) of t-BuOH. The ketone, 1 (60 g, 0.28 mol) was dissolved in 600 mL of THF and added to the stirred mixture at room temperature. A yellow precipitate formed and the mixture was stirred for 1 h. N-benzyloxycarbonyl-glycinyl N-hydroxysuccinimide (128.6 g, 0.42 mol) was dissolved in 600 mL of THF and added dropwise at r.t. over 1 h. The mixture was stirred for another 5 minutes and 150 mL of water was added. The pH was adjusted to 6.7 with 70 mL of AcOH. Hydrazine monohydrate (41 mL in 100 mL of water) was added via an addition funnel. The mixture was stirred for 1 h and was diluted with 500 mL of water and 500 mL of ethyl acetate. The biphasic mixture was transferred to a sep funnel and the layers were separated. The aqueous layer was extracted with EtOAc (3×300 mL). The organic layer was dried (Na2SO4), filtered and evaporated to leave 157 g of a crude reddish oil.

Aufarbeitung

  1. customA 3 L round bottom flask fitted with a mechanical stirrer, N2 inlet and an addition funnel
  2. additionadded to the stirred mixture at room temperature
  3. customA yellow precipitate formed
  4. additionadded dropwise at r.t. over 1 h
  5. stirringThe mixture was stirred for another 5 minutes
  6. stirringThe mixture was stirred for 1 h
  7. customThe biphasic mixture was transferred to a sep funnel
  8. customthe layers were separated
  9. extractionThe aqueous layer was extracted with EtOAc (3×300 mL)
  10. dry with materialThe organic layer was dried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-16ac67abf21f439ca2c6dc20851ec3b4
Quelldatensatz
uspto-grants-2003_09
Patentnummer
US06617324B1

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