1,2-Dichlorobenzene → (1R,2S,3S,4R,5S)-5-[4-chloro-3-[[4-(2,2,2-trifluoroethoxyl)phenyl]methyl]phenyl]-1-(1-hydroxyethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol

HRID 1055556Notes

Reaction equation

HRID 1055556 reaction equation
C([O:8][C@H:9]1[C@H:15]([O:16]CC2C=CC=CC=2)[C@@H:14]([O:24]CC2C=CC=CC=2)[C@:13]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH2:48][C:49]([F:52])([F:51])[F:50])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:53]([OH:55])[CH3:54])[CH2:11][O:12]2)C1C=CC=CC=1.ClC1C=CC=CC=1Cl>[Pd].CO.O1CCCC1>[Cl:39][C:36]1[CH:37]=[CH:38][C:33]([C@@:13]23[O:32][C@@:10]([CH:53]([OH:55])[CH3:54])([CH2:11][O:12]2)[C@@H:9]([OH:8])[C@H:15]([OH:16])[C@H:14]3[OH:24])=[CH:34][C:35]=1[CH2:40][C:41]1[CH:46]=[CH:45][C:44]([O:47][CH2:48][C:49]([F:51])([F:50])[F:52])=[CH:43][CH:42]=1

Participants

5

Reactant 2

HCID 72391,2-DichlorobenzeneHCID 1183777981-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoroethoxyl)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol

Product 1

HCID 117986010(1R,2S,3S,4R,5S)-5-[4-chloro-3-[[4-(2,2,2-trifluoroethoxyl)phenyl]methyl]phenyl]-1-(1-hydroxyethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triolYield 31%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of 1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoroethoxyl) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol 17n (350.0 mg, 0.45 mmol) in a methanol/tetrahydrofuran mixture (v/v=4/1, 15 mL) were added o-dichlorobenzene (0.25 mL, 2.25 mmol) and 10% Pd/C (50.0 mg, 0.04 mmol) at room temperature. The mixture was stirred at room temperature under H2 for 3 hours and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=3/1 to give a few white solid. Then the solid was further purified by prep-HPLC to give the title compound 17 as a white solid (70.5 mg, 30.7%, HPLC: 90.5%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 505.20 [M+H]+; and 1H NMR (600 MHz, DMSO-d6) δ(ppm): 7.41 (m, 2H), 7.31 (d, 1H), 7.15 (d, 2H), 6.97 (d, 2H), 5.31 (m, 1H), 4.85 (m, 2H), 4.68 (m, 2H), 4.64 (d, 1H), 4.02 (m, 1H), 3.98 (d, 2H), 3.83 (q, 1H), 3.76 (d, 1H), 3.54 (m, 1H), 3.43 (m, 2H), 1.16 (d, 3H).

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by silica gel chromatography
  4. washeluted with PE/EtOAc(v/v)=3/1
  5. customto give a few white solid
  6. customThen the solid was further purified by prep-HPLC

Sources & evidence

ORD record
ord-93ffc6a4fa6f4d2580de6b598c39ffce
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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