Sodium Hydroxide → 1,1-Dimethylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

HRID 423520Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 423520
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[CH:12][C:11]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)=[CH:10][CH:9]=2)=[C:4]([F:29])[CH:3]=1.[Na+].[CH3:31][S:32]([O-:34])=[O:33].N1CCC[C@H]1C(O)=O.[OH-].[Na+]>CS(C)=O>[F:29][C:4]1[CH:3]=[C:2]([S:32]([CH3:31])(=[O:34])=[O:33])[CH:7]=[CH:6][C:5]=1[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)=[CH:10][CH:9]=1

Komponenten

6

Edukt 4

HCID 14798Sodium HydroxideHCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 666731501,1-Dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate

Produkt 1

HCID 249943361,1-Dimethylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylateAusbeute 29,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A mixture of 1,1-dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate (0.214 g, 0.46 mmol), methanesulfinic acid sodium salt (71 mg, 80%, 0.55 mmol), L-proline (11 mg, 0.09 mmol), Cul (9 mg, 0.05 mmol) and NaOH (4 mg, 0.09 mmol) in DMSO (2.5 mL) was degassed, purged with N2 and heated at 110° C. for 48 h. The mixture was cooled to ambient temperature and was poured into water and extracted with EtOAc. The combined organic extract was washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a yellow solid. The crude product was purified by chromatography on a silica gel column eluted with 25% EtOAc/CH2Cl2 to give 62.5 mg (29%) of the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.40 (d, 1H, J=3.0 Hz), 8.15-8.10 (m, 1H), 7.90-7.75 (m, 3H), 7.50 (dd, 1H, Ja=8.8 Hz, Jb=2.9 Hz), 4.20-4.10 (m, 2H), 4.00 (d, 2H, J=6.4 Hz), 3.18 (s, 3H), 2.90-2.75 (m, 2H), 2.15-2.00 (m, 1H), 1.90-1.80 (m, 2H), 1.46 (s, 9H), 1.40-1.25 (m, 2H); LRMS (ESI), m/z 465 (M+H).

Aufarbeitung

  1. customwas degassed
  2. custompurged with N2
  3. temperatureThe mixture was cooled to ambient temperature
  4. additionwas poured into water
  5. extractionextracted with EtOAc
  6. extractionThe combined organic extract
  7. washwas washed with water and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customto give the crude product as a yellow solid
  12. customThe crude product was purified by chromatography on a silica gel column
  13. washeluted with 25% EtOAc/CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-44fa203d699643f8b7f34096bbc01576
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101634B2

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