(Dimethyl sulfide)trihydroboron → (4R,9aR)-6-(1-(S)-Hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 11949

Reaktionsgleichung

Reaktionsgleichung von HRID 11949
B.[CH3:2]SC.[C:5]([O:9][C:10]([N:12]1[CH2:24][C@@H:23]([CH3:25])[N:22]2[C@H:14]([CH2:15][C:16]3[C:21]2=[N:20][C:19]([CH2:26][O:27]CCO)=[CH:18][CH:17]=3)[CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]>C1COCC1>[C:5]([O:9][C:10]([N:12]1[CH2:24][C@@H:23]([CH3:25])[N:22]2[C@H:14]([CH2:15][C:16]3[C:21]2=[N:20][C:19]([C@@H:26]([OH:27])[CH3:2])=[CH:18][CH:17]=3)[CH2:13]1)=[O:11])([CH3:6])([CH3:7])[CH3:8]

Komponenten

4

Edukt 2

HCID 12423031(Dimethyl sulfide)trihydroboronHCID 69557393(4R,9aR)-6-(2-hydroxy-ethoxymethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester2×

Produkt 1

HCID 69357459(4R,9aR)-6-(1-(S)-Hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a stirred solution of (R)-Me-CBS-oxazaborolidine (770 μl, 1M in toluene) in THF (3 ml) was added borane-dimethylsulfide (770 μl, 2M in THF) at 0° C. under nitrogen. A solution was stirred for 5 mins, then 6-acetyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 34, intermediate b) (255 mg) in THF (2.5 ml) was added dropwise over 45 mins. A solution was stirred at 0° C. for 3 hours, quenched with methanol and partitioned between aqueous ammonium chloride and EtOAc. The phases were separated and the organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography [SiO2; isohexane-ethyl acetate (1:1)] to afford 6-((1S)-1-hydroxy-ethyl)-(4R,9aR)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (185 mg) as a colorless oil: 1H NMR (400 MHz, CDCl3): 7.16 (1H, d, J 7 Hz), 6.35 (1H, d, J 7 Hz), 4.37–4.31 (1H, br s), 4.31–4.19 (1H, br s), 4.09–3.95 (1H, m), 3.95–3.85 (1H, m), 3.13–2.94 (2H, m), 2.79–2.55 (1H, br s), 2.54 (1H, dd, J 6 and 16 Hz), 1.48 (9H, s), 1.44 (3H, d, J 6.5 Hz) and 1.24 (3H, d, J 6.5 HZ); MS (ES) 334.3 (MH+).

Aufarbeitung

  1. stirringA solution was stirred at 0° C. for 3 hours
  2. customquenched with methanol
  3. custompartitioned between aqueous ammonium chloride and EtOAc
  4. customThe phases were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography [SiO2; isohexane-ethyl acetate (1:1)]

Quellen und Nachweise

ORD-Eintrag
ord-192ecfe2801b42658ad839c2a4bd0c17
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07098337B2

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