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

HRID 1055542Notes

Reaction equation

HRID 1055542 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][C:48]([F:51])([F:50])[F:49])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:52]([OH:54])[CH3:53])[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:52]([OH:54])[CH3:53])([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][C:48]([F:50])([F:49])[F:51])=[CH:43][CH:42]=1

Participants

5

Reactant 2

HCID 72391,2-DichlorobenzeneHCID 1183778041-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol

Product 1

HCID 117986012(1R,2S,3S,4R,5S)-5-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-1-(1-hydroxyethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triolYield 28.2%

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-[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol 15q (102 mg, 0.13 mmol) in a methanol/tetrahydrofuran mixture (v/v=4/1, 10 mL) were added o-dichlorobenzene (95 mg, 0.65 mmol) and 10% Pd/C (41 mg, 0.39 mmol) at room temperature. The mixture was stirred under H2 at room temperature for 2 hours and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=1/5 to give the title compound 15 as a white solid (18 mg, 28.2%, HPLC: 96.2%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 535.2[M+HCOO]−; and 1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.47 (d, 1H), 7.42 (d, 1H), 7.37-7.26 (m, 5H), 5.27 (d, 1H), 4.92 (m, 2H), 4.61 (d, 1H), 4.12 (s, 2H), 4.01 (dd, 1H), 3.81 (dd, 1H), 3.54 (d, 1H), 3.47-3.37 (m, 3H), 1.17 (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)=1/5

Sources & evidence

ORD record
ord-004a436f44fe49c690430b75514458ee
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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