Ethyl bromoacetate → ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate

HRID 1839554Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1839554
Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[F:8][C:9]1[CH:10]=[C:11]([OH:23])[CH:12]=[C:13]([C:15]2([O:21][CH3:22])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:14]=1.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[F:8][C:9]1[CH:10]=[C:11]([CH:12]=[C:13]([C:15]2([O:21][CH3:22])[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)[CH:14]=1)[O:23][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4]

Komponenten

5

Edukt 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 117362763-Fluoro-5-(4-methoxytetrahydro-2H-pyran-4-yl)phenol

Produkt 1

HCID 22246123ethyl 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetateAusbeute 73,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of ethyl bromoacetate (0.5 g, 3 mmol), 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenol (Example 8, Step 4) (0.3 g, 1.3 mmol) and K2CO3 (0.11 g, 0.8 mmol) in dimethylformamide (5.0 mL) was stirred at room temperature for 16 h under an argon atmosphere. The reaction mixture was partitioned between 5% citric acid (25 mL) and EtOAc (25 mL). The organic phase was washed with water, dried (Na2SO4), filtered and concentrated. The resulting syrup was purified by flash column chromatography on silica gel, eluting with 25% EtOAc in hexane, to give 0.3 g (73%) of ethyl 3-fluoro-5(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxyacetate as a colorless viscous liquid: 1H NMR (CDCl3/300 MHz) δ 6.77 (d,2H, J=10.5 Hz), 6.52 (d, 1H, J=10.5 Hz), 4.61 (s, 2H), 4.28 (q, 2H, J=6.9 Hz), 3.82 (m, 4H), 2.99 (s, 3H), 1.92 (m, 4H), 1.31 (t, 3H, J=6.9 Hz). FABMS m/z=313 (M+H). HRMS calcd for C16H22FO5313.1451, found 313.1399.

Aufarbeitung

  1. customThe reaction mixture was partitioned between 5% citric acid (25 mL) and EtOAc (25 mL)
  2. washThe organic phase was washed with water
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting syrup was purified by flash column chromatography on silica gel
  7. washeluting with 25% EtOAc in hexane

Quellen und Nachweise

ORD-Eintrag
ord-18b9955c36b04114982ad16af4260a14
Quelldatensatz
uspto-grants-2004_01
Patentnummer
US06677364B2

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