Isopropanol → 1-benzyl-1'-isopropyl-1'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-one

HRID 536288

Reaktionsgleichung

Reaktionsgleichung von HRID 536288
[CH2:1]([N:8]1[CH2:22][CH2:21][C:11]2([O:19][C:18]3[CH:17]=[N:16][NH:15][C:14]=3[C:13](=[O:20])[CH2:12]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][CH:24](O)[CH3:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1>O1CCCC1>[CH2:1]([N:8]1[CH2:22][CH2:21][C:11]2([O:19][C:18]3[CH:17]=[N:16][N:15]([CH:24]([CH3:25])[CH3:23])[C:14]=3[C:13](=[O:20])[CH2:12]2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

6

Edukt 4

HCID 3776IsopropanolHCID 11776TriphenylphosphineHCID 5387121Dibenzyl azodicarboxylateHCID 68065450HCID 68065450, Verbindung

Produkt 1

HCID 680661841-benzyl-1'-isopropyl-1'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-oneAusbeute 39,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

1-Benzyl-1′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-7′(6′H)-one (204 mg, 0.67 mmol) was dissolved in 10 mL tetrahydrofuran. 2-propanol (0.11 mL, 1.37 mmol) and polymer supported triphenylphosphine (0.5 g, 3 mmol/g loading) were added followed by addition of DBAD (322 mg, 1.37 mmol) and stirred at ambient temperature for 5 days. Filtered off polymer supported triphenyl phosphine and washed filtercake with 100 mL ethyl acetate. The filtrate was concentrated and the resultant yellow oil was treated with 10 mL 4N HCl/dioxane. The mixture was stirred 1 h at ambient temperature. The volatiles were removed under reduced pressure. The resultant sludge was partitioned between 50 mL sat aq. sodium bicarbonate and 50 mL ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed (30-100% ethyl acetate/heptane gradient, 10 g silica) to yield 90 mg (35%) of 1-benzyl-1′-isopropyl-1′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-7′(6′H)-one as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.30 (m, 3H), 7.24 (m, 2H), 7.18 (s, 1H), 5.14 (spt, 1H), 3.52 (s, 2H), 2.60 (m, 4H), 2.41 (td, J=11.6, 2.5 Hz, 2H), 2.06 (d, J=12.5 Hz, 2H), 1.71 (m, 2H), 1.44 (m, 6H): m/z (M+1)=340.5.

Aufarbeitung

  1. additionwere added
  2. filtrationFiltered off polymer
  3. washwashed filtercake with 100 mL ethyl acetate
  4. concentrationThe filtrate was concentrated
  5. additionthe resultant yellow oil was treated with 10 mL 4N HCl/dioxane
  6. stirringThe mixture was stirred 1 h at ambient temperature
  7. customThe volatiles were removed under reduced pressure
  8. customThe resultant sludge was partitioned between 50 mL
  9. dry with materialThe organic phase was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customchromatographed (30-100% ethyl acetate/heptane gradient, 10 g silica)

Quellen und Nachweise

ORD-Eintrag
ord-3693de78ce8440fbb571e5a03e0b1d5e
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08859577B2

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