1-(4-(S),5-(S)-Bis-benzyloxy-6-(R)-benzyloxymethyl-3-(R)-hydroxy-tetrahydro-pyran-2-(R)-yl)-3-(S)-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one → 3-(S)-(5-Chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1-(3-(R),4-(S),5-(S)-trihydroxy-6-(R)-hydroxymethyl-tetrahydro-pyran-2-(R)-yl)-1,3-dihydro-indol-2-one

HRID 895806Notes

Reaction equation

HRID 895806 reaction equation
C([O:8][C@@H:9]1[C@@H:14]([O:15]CC2C=CC=CC=2)[C@@H:13]([CH2:23][O:24]CC2C=CC=CC=2)[O:12][C@@H:11]([N:32]2[C:40]3[C:35](=[CH:36][CH:37]=[C:38]([C:41]([F:44])([F:43])[F:42])[CH:39]=3)[C@@:34]([C:46]3[CH:51]=[C:50]([Cl:52])[CH:49]=[CH:48][C:47]=3[O:53][CH3:54])([F:45])[C:33]2=[O:55])[C@@H:10]1[OH:56])C1C=CC=CC=1>[Pt]=O.C(OCC)(=O)C>[Cl:52][C:50]1[CH:49]=[CH:48][C:47]([O:53][CH3:54])=[C:46]([C@@:34]2([F:45])[C:35]3[C:40](=[CH:39][C:38]([C:41]([F:42])([F:43])[F:44])=[CH:37][CH:36]=3)[N:32]([C@H:11]3[C@H:10]([OH:56])[C@@H:9]([OH:8])[C@H:14]([OH:15])[C@@H:13]([CH2:23][OH:24])[O:12]3)[C:33]2=[O:55])[CH:51]=1

Participants

4

Reactant 1

HCID 208124891-(4-(S),5-(S)-Bis-benzyloxy-6-(R)-benzyloxymethyl-3-(R)-hydroxy-tetrahydro-pyran-2-(R)-yl)-3-(S)-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one

Product 1

HCID 208124903-(S)-(5-Chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1-(3-(R),4-(S),5-(S)-trihydroxy-6-(R)-hydroxymethyl-tetrahydro-pyran-2-(R)-yl)-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 2

HCID 82844Platinum oxide (PtO)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask containing 1-(4-(S),5-(S)-Bis-benzyloxy-6-(R)-benzyloxymethyl-3-(R)-hydroxy-tetrahydro-pyran-2-(R)-yl)-3-(S)-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one ((S)-VIII) (0.144 g, 0.18 mmol) was added ethyl acetate (1 mL). Platinum oxide (0.020 g, 0.09 mmol) was added to the reaction mixture which was then placed under a hydrogen atmosphere. The reaction was allowed to stir at room temperature overnight. The crude reaction mixture was purified via reverse phase column chromatography (C18, 1:1 water:acetonitrile). The title product was obtained as a white solid (0.040 g, 42%). 1H NMR (MeOH-D4, 400 MHz): δ 7.73 (dd, 1H, J=1.6 Hz, 0.9 Hz), 7.52 (s, 1H), 7.39 (m, 2H), 7.30 (dd, 1H, J=5.5 Hz, 2.0 Hz), 6.94 (dd, 1H, J=7.5 Hz, 1.2 Hz), 5.43 (d, 1H, J=9.5 Hz), 4.04 (t, 1H, J=9.1 Hz), 3.95 (dd, 1H, J=10.5 Hz, 1.4 Hz), 3.75 (dd, 1H, J=6.8 Hz, 5.3 Hz), 3.57 (s, 3H), 3.53 (m, 2H); 19F NMR (MeOH-D4, 376 MHz): δ−64.6, −161.7; LRMS: 519 [M−H]−.

Workup

  1. customThe crude reaction mixture
  2. customwas purified via reverse phase column chromatography (C18, 1:1 water:acetonitrile)

Sources & evidence

ORD record
ord-1ffdc0bc43784714a184ccba0fd9d1f3
Source dataset
uspto-grants-2005_07
Patent number
US06916937B2

Reaction notes

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