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Hydrochloric Acid → Methyl 1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-alpha-D-glucopyranoside

HRID 1470054
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1470054
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)[CH:3]=1.[Li][CH2:20]CCC.C[Si](C)(C)[O:26][C@@H:27]1[C@@H:32]([O:33][Si](C)(C)C)[C@H:31]([O:38][Si](C)(C)C)[C@@H:30]([CH2:43][O:44][Si](C)(C)C)[O:29][C:28]1=[O:49].Cl.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.C1(C)C=CC=CC=1.CO>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C@@:28]2([O:49][CH3:20])[C@H:27]([OH:26])[C@@H:32]([OH:33])[C@H:31]([OH:38])[C@@H:30]([CH2:43][OH:44])[O:29]2)=[CH:3][C:4]=1[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 99964494-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzeneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 178418339Butyllithium

Produkt 1

HCID 24807437
Methyl 1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-alpha-D-glucopyranoside

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 1140TolueneLösungsmittelHCID 22635083Tetrahydrofuran tolueneLösungsmittel

Reaktionsbedingungen

Temperatur
-65 °C

Versuchsvorschrift

To a solution of Example 1B (200 g, 0.614 mol) in anhydrous toluene/THF (1.2 L, 2:1 (v/v)) was added n-BuLi (2.5 M in hexane, 295 mL) dropwise at −65° C. The reaction was stirred at −65° C. for 30 min. Then the mixture was transferred by a cannula to a solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one) (373 g, 0.798 mol) in toluene (1.2 L) at −65° C. The mixture was stirred at −65° C. until starting material was consumed (2 h). The reaction was quenched with hydrochloric acid (36˜38%, 113 mL, 1.35 mol) in methanol (800 mL), and stirred at room temperature overnight. The reaction was neutralized with saturated sodium bicarbonate to pH 7.5 and the organic phase was separated and the aqueous phase was extracted with ethyl acetate (2×3.0 L). The combined organic layers were washed with brine (2×2.0 L), dried over sodium sulfate and concentrated. The residue was dissolved in hot toluene (600 mL) and poured into n-hexane (2.0 L) with vigorous stirring. After stirring for 1 h, the mixture was filtered and the filter cake was dried under vacuum to give the desired product as a white solid. This solid was used without further purification in the next step. MS ESI (m/z) 439 [M+1]+.

Aufarbeitung

  1. customat −65° C
  2. stirringThe mixture was stirred at −65° C.
  3. customwas consumed (2 h)
  4. stirringstirred at room temperature overnight
  5. customthe organic phase was separated
  6. extractionthe aqueous phase was extracted with ethyl acetate (2×3.0 L)
  7. washThe combined organic layers were washed with brine (2×2.0 L)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in hot toluene (600 mL)
  11. additionpoured into n-hexane (2.0 L) with vigorous stirring
  12. stirringAfter stirring for 1 h
  13. filtrationthe mixture was filtered
  14. customthe filter cake was dried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-e789103d11544b41bdc0144f204e3ec9
Quelldatensatz
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09006403B2

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