Diethyl Oxalate → Ethyl 2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetate

HRID 245411Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245411
[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]([F: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.[C:41](OCC)(=[O:47])[C:42]([O:44][CH2:45][CH3:46])=[O:43]>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]([F:34])[C:23]([F:35])=[C:22]([C:41](=[O:47])[C:42]([O:44][CH2:45][CH3:46])=[O:43])[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 7268Diethyl OxalateHCID 67357593(2R,6S)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine2×HCID 178418400CID 53628100

Produkt 1

HCID 86658065Ethyl 2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetateAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

(2R,6S)-4-[6-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-2,3-difluorophenyl]-2,6-dimethylmorpholine (Intermediate 3, 0.5 g, 1.01 mmol) was dissolved in 10 ml of THF and cooled to −78° C. Sec-butyl lithium (1.358 ml, 1.77 mmol) was added drop wise over 5 minutes. The reaction stirred at −78° C. for 1.5 hours. The reaction mixture was cannulated into a −78° C. cooled flask containing diethyl oxalate (1.370 ml, 10.09 mmol) in 10 ml of THF. The reaction was allowed to stir at −78° C. for 30 minutes; quenched cold with 1 ml sat NH4Cl and allowed to warm to room temp. The reaction was diluted with water and extracted twice with ethyl acetate. The organic layers were combined and washed twice with brine, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography using a gradient of hexanes to ethyl acetate to give the title compound (486 mg, 81% yield) contaminated with diethyl oxalate. This material was taken to the next step without further purification.

Aufarbeitung

  1. customwas cannulated into a −78° C.
  2. temperaturecooled flask
  3. stirringto stir at −78° C. for 30 minutes
  4. customquenched cold with 1 ml
  5. temperatureto warm to room temp
  6. additionThe reaction was diluted with water
  7. extractionextracted twice with ethyl acetate
  8. washwashed twice with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-4ed62c79324b489482889a28716d7bd2
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658641B2

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