4-Toluenesulfonyl chloride → [2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methyl 4-methylbenzenesulfonate

HRID 2056366

Reaktionsgleichung

Reaktionsgleichung von HRID 2056366
[CH3:1][C:2]1[O:3][C:4]2[C:10]3[O:11][C@@H:12]([CH2:15][OH:16])[CH2:13][O:14][C:9]=3[CH:8]=[CH:7][C:5]=2[N:6]=1.[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:27][C:17]1[CH:22]=[CH:21][C:20]([S:23]([O:16][CH2:15][CH:12]2[CH2:13][O:14][C:9]3[CH:8]=[CH:7][C:5]4[N:6]=[C:2]([CH3:1])[O:3][C:4]=4[C:10]=3[O:11]2)(=[O:25])=[O:24])=[CH:19][CH:18]=1

Komponenten

6

Edukt 3

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 69017866[(8S)-2-methyl-7,8-dihydro[1,4]dioxino[2,3-g)[1,3]benzoxazol-8-yl]methanol

Produkt 1

HCID 11268854[2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methyl 4-methylbenzenesulfonate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

To a solution of [(8S)-2-methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methanol (1.80 g, 8.14 mmole) in methylene chloride (100 mL) was added p-toluenesulfonyl chloride (3.90 g, 20.4 mmole). The mixture was cooled in an ice bath and a solution of diisopropylethylamine (3.55 mL, 20.4 mmole) in methylene chloride (20 mL) was then added dropwise, followed by 4-dimethylaminopyridine (0.65 g, 5.30 mmole). The solution was allowed to warm to room temperature and was stirred under nitrogen overnight. The reaction was diluted to 500 mL in volume with methylene chloride, then washed with aqueous 2 N HCl (200 mL), with saturated aqueous sodium bicarbonate (200 mL), and with brine (150 mL), dried over magnesium sulfate, filtered and evaporated in vacuum to a yellow oil. The crude oil was column chromatographed on silica gel using methylene chloride to remove impurities and 3% methanol/methylene chloride to elute the (R)-enantiomer of the title compound, which becomes a white solid under vacuum (2.56 g, 84%), m.p. 123° C. MS (ESI) m/z 376 (M+H)+.

Aufarbeitung

  1. temperatureThe mixture was cooled in an ice bath
  2. washwashed with aqueous 2 N HCl (200 mL), with saturated aqueous sodium bicarbonate (200 mL)
  3. dry with materialwith brine (150 mL), dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuum to a yellow oil
  6. customchromatographed on silica gel
  7. customto remove impurities and 3% methanol/methylene chloride
  8. washto elute the (R)-enantiomer of the title compound, which

Quellen und Nachweise

ORD-Eintrag
ord-d16aceb1b5134184b08f4cb26ed9a931
Quelldatensatz
uspto-grants-2008_02
Patentnummer
US07335666B2

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