2-Pyridinecarboxaldehyde → {5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-chloro-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2-fluorophenyl}(pyridin-2-yl)methanol

HRID 245385

Reaktionsgleichung

Reaktionsgleichung von HRID 245385
[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([Cl:34])[C:23]([F:35])=[CH:22][CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])(CC)C.[N:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[CH:47]=[O:48]>C1COCC1>[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([Cl:34])[C:23]([F:35])=[C:22]([CH:47]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][N:41]=2)[OH:48])[CH:21]=1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Komponenten

5

Edukt 3

HCID 142732-PyridinecarboxaldehydeHCID 67359669(2R,6S)-[6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-chloro-3-fluorophenyl]-2,6-dimethylmorpholine2×HCID 178418400CID 53628100

Produkt 1

HCID 86717851{5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-chloro-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2-fluorophenyl}(pyridin-2-yl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a stirred solution of (2R,6S)-[6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-chloro-3-fluorophenyl]-2,6-dimethylmorpholine (Intermediate 42, 2.0 g, 3.9 mmol) in anhydrous THF (10 mL), sec-Butyl lithium (1.4 M in cyclohexane, 2.1 eq) was added and the solution was stirred for ½ h at −78° C. Pyridine-2-carbaldehyde (0.74 mL, 7.8 mmol) in THF (5 mL) was added dropwise and the solution was stirred for additional 1 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulphate. The solvent was removed under vacuum and the residue was purified over silica gel chromatography column using ethyl acetate-pet. ether gradient to obtain product. Yield: 900 mg, (37%)

Aufarbeitung

  1. stirringthe solution was stirred for additional 1 h
  2. customThe reaction mixture was quenched with saturated ammonium chloride solution
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulphate
  6. customThe solvent was removed under vacuum
  7. customthe residue was purified over silica gel chromatography column
  8. customto obtain product

Quellen und Nachweise

ORD-Eintrag
ord-870d5a38576941dba0f40eea2b5409f1
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658641B2

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