Trimethyl orthoformate → N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(1,1,3,3-tetramethoxypropan-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 2168297Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2168297
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:31])=[C:6]([C@:8]23[CH2:17][O:16][C@@H:15](/[CH:18]=[CH:19]/[O:20][CH3:21])[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:22][C:23](=[O:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:9]3)[CH:7]=1.[CH:32](OC)([O:35][CH3:36])[O:33][CH3:34].[C:39](=O)(O)[O-:40].[Na+]>ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:31])=[C:6]([C@:8]23[CH2:17][O:16][C@@H:15]([CH:18]([CH:32]([O:35][CH3:36])[O:33][CH3:34])[CH:19]([O:40][CH3:39])[O:20][CH3:21])[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:22][C:23](=[O:30])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[N:9]3)[CH:7]=1

Komponenten

5

Edukt 3

HCID 9005Trimethyl orthoformateHCID 516892Sodium BicarbonateHCID 86762662N-{(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-[(E)-2-methoxyethenyl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl}benzamide

Produkt 1

HCID 86762663N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(1,1,3,3-tetramethoxypropan-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of N-{(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-[(E)-2-methoxyethenyl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl}benzamide (C43) (0.54 g, 1.1 mmol) in dichloromethane (2 mL) at 0° C., was added trimethyl orthoformate (0.239 mL, 2.19 mmol) followed by drop-wise addition of boron trifluoride-diethyl etherate (0.136 mL, 1.08 mmol), without letting the reaction temperature exceed 3° C. The resulting solution was allowed to stir at the same temperature for 1.5 hours. The reaction mixture was diluted with dichloromethane (200 mL) and a saturated aqueous solution of sodium bicarbonate (200 mL). The organic layer was separated and resulting aqueous layer was extracted with further dichloromethane (200 mL). The combined organics were washed with brine (200 mL), dried over sodium sulfate, filtered and concentrated to give the product (0.65 g) as a white solid, which was taken directly to the following step. 1H NMR (400 MHz, CD3OD) characteristic peaks: δ 8.23 (br d, J=7.0 Hz, 2H), 7.41-7.52 (m, 5H), 6.99 (dd, J=1.7, 9.0 Hz, 1H), 4.52 (dd, J=17.7, 4.2 Hz, 1H), 4.13 (d, J=12.5 Hz, 1H), 4.04 (d, J=8.4 Hz, 1H), 3.79 (d, J=11.9 Hz, 1H), 3.13-3.19 (m, 1H), 2.98 (dd, J=13.1, 2.7 Hz, 1H), 2.64 (dd, J=13.1, 1.3 Hz, 1H).

Aufarbeitung

  1. customexceed 3° C
  2. customThe organic layer was separated
  3. customresulting aqueous layer
  4. extractionwas extracted with further dichloromethane (200 mL)
  5. washThe combined organics were washed with brine (200 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-f2511c6e173b4c88a3947b4c8c6c8b7b
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045498B2

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