Potassium Phosphate, Tribasic → Tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate

HRID 1849783Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1849783
[C:1]12([CH2:8][O:9][C:10]3[C:22](Cl)=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[C:12]([F:24])[CH:11]=3)[CH2:7][CH:6]1[CH2:5][CH2:4][CH2:3][CH2:2]2.[CH:25]1(B(O)O)[CH2:27][CH2:26]1.F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]12([CH2:8][O:9][C:10]3[C:22]([CH:25]4[CH2:27][CH2:26]4)=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[C:12]([F:24])[CH:11]=3)[CH2:7][CH:6]1[CH2:5][CH2:4][CH2:3][CH2:2]2

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703665Tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-chloro-2-fluorobenzoate

Produkt 1

HCID 86703666Tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoateAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

In a sealed tube containing tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-chloro-2-fluorobenzoate (1.30 g, 3.70 mmol), cyclopropylboronic acid (0.47 g, 5.50 mmol), tricyclohexylphosphine tetrafluoroborate (0.27 g, 0.74 mmol) and palladium acetate (0.08 g, 0.37 mmol) and potassium phosphate (3.13 g, 14.8 mmol) in toluene (20 mL) and water (2.0 mL) was bubbled with a nitrogen atmosphere for 10 minutes. The reaction mixture was heated to 140° C. for 6 hours and cooled to ambient temperature. The solvent was concentrated in vacuo to dryness. The crude residue was purified column chromatography (10% gradient ethyl acetate in hexanes) afforded the title compound as a colorless solid (1.00 g, 75%): 1H NMR (300 MHz, CDCl3) 7.37 (d, J=8.5 Hz, 1H), 6.42 (d, J=12.8 Hz, 1H), 3.61 (d, J=9.1 Hz, 1H), 3.78 (d, J=9.1 Hz, 1H), 1.96-1.52 (m, 7H), 1.55 (s, 9H), 0.92-0.82 (m, 4H), 0.67-0.61 (m, 4H), 0.38-0.33 (m, 1H).

Aufarbeitung

  1. customwas bubbled with a nitrogen atmosphere for 10 minutes
  2. temperaturecooled to ambient temperature
  3. concentrationThe solvent was concentrated in vacuo to dryness
  4. customThe crude residue was purified column chromatography (10% gradient ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-41906bff08654de1af0bb5341bf14897
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952169B2

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