Trifluoromethanesulfonic acid, lithium salt → methyl (2R)-3-{[4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenyl]amino}-2-hydroxypropanoate

HRID 896160

Reaktionsgleichung

Reaktionsgleichung von HRID 896160
[O:1]=[S:2]1(=[O:17])[CH2:7][CH2:6][N:5]([C:8]2[C:14]([F:15])=[CH:13][C:11]([NH2:12])=[CH:10][C:9]=2[F:16])[CH2:4][CH2:3]1.[O-]S(C(F)(F)F)(=O)=O.[Li+].[O:27]1[CH2:33][C@@H:28]1[C:29]([O:31][CH3:32])=[O:30]>C(#N)C>[O:17]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([C:8]2[C:14]([F:15])=[CH:13][C:11]([NH:12][CH2:33][C@@H:28]([OH:27])[C:29]([O:31][CH3:32])=[O:30])=[CH:10][C:9]=2[F:16])[CH2:4][CH2:3]1

Komponenten

5

Edukt 3

HCID 3664839Trifluoromethanesulfonic acid, lithium saltHCID 9877347Methyl (2R)-2-oxiranecarboxylateHCID 98999344-(4-Amino-2,6-difluorophenyl)-1lambda~6~,4-thiazinane-1,1-dione

Produkt 1

HCID 86610079methyl (2R)-3-{[4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenyl]amino}-2-hydroxypropanoateAusbeute 57 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A solution of 4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluoroaniline (EXAMPLE 15, Step 3, 1.30 g, 5.0 mmol) in acetonitrile (7.5 mL) is treated with lithium triflate (0.60 g, 5.0 mmol) and methyl (2R)-2,3-epoxypropanoate (0.51 g, 0.46 mL, 5.0 mmol) and heated to 70° C. for 2 h. At this time an additional amount (1.5 mmol each) of the two reagents is added and the mixture stirred for another 7 h at 70° C. The reaction mixture is then cooled to room temperature, concentrated, and purified by column chromatography (50→60% ethyl acetate-hexane) to provide the title compound (1.03 g, 57%), MS (m/z): [M+H]+=365; 1H NMR (300 MHz, CDCl3): δ 3.04 (d, 1H), 3.15 (m, 4H), 3.31-3.46 (m, 2H), 3.47-3.56 (m, 4H), 3.83 (s, 3H), 4.20 (t, 1H), 4.40 (m, 1H), 6.17 (d, 2H).

Aufarbeitung

  1. temperatureThe reaction mixture is then cooled to room temperature
  2. concentrationconcentrated
  3. custompurified by column chromatography (50→60% ethyl acetate-hexane)

Quellen und Nachweise

ORD-Eintrag
ord-c00a8558a16f440281427e97e0d403cd
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06919329B2

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