Sodium Bicarbonate → Tert-butyl 8-(2,2-difluoroethyl)-10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72888

Reaktionsgleichung

Reaktionsgleichung von HRID 72888
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]1[O:24][C:11]2([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[CH2:10][NH:9][CH2:8]1.C(=O)([O-])O.[Na+].FC(F)(F)S(O[CH2:36][CH:37]([F:39])[F:38])(=O)=O>C(O)C.C(Cl)Cl>[F:38][CH:37]([F:39])[CH2:36][N:9]1[CH2:8][CH:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[O:24][C:11]2([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:13][CH2:12]2)[CH2:10]1

Komponenten

6

Edukt 3

HCID 516892Sodium BicarbonateHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 70872717tert-Butyl 2-(pyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Produkt 1

HCID 86672472Tert-butyl 8-(2,2-difluoroethyl)-10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To tert-butyl 10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (63 mg, 0.19 mmol) in ethanol was added sodium hydrogen carbonate (64 mg, 0.76 mmol) followed by the addition of 2,2-difluoroethyl trifluoromethanesulfonate (49 mg, 0.23 mmol) and reaction mixture was heated at 80° C. for 40 minutes. The reaction mixture was cooled to room temperature and diluted with DCM and the organic layer was washed with 1:1 NaOH:NaHCO3 solution. The organics were separated, dried over Na2SO4, filtered and concentrated in vacuo to give tert-butyl 8-(2,2-difluoroethyl)-10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate as an oil. To the oil was added HCl (237.5 μL of 4 M in dioxane, 0.95 mmol) at room temperature under an atmosphere of nitrogen and the reaction mixture was stirred for 30 minutes. The solvent was removed in vacuo and the residue was triturated with ether to give 8-(2,2-difluoroethyl)-10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane (45 mg, 79%). ESI-MS m/z calc. 297.3. Found 298.4 (M+1)+; Retention time: 0.35 minutes (3 min run).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washthe organic layer was washed with 1:1 NaOH
  3. customThe organics were separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-c855550fa8304214ac8abef28b86a278
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08828996B2

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