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

HRID 1913079Notes

Reaction equation

HRID 1913079 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][CH:49]([F:51])[F:50])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH2:52][OH:53])[CH2:11][O:12]2)C1C=CC=CC=1.ClC1C=CC=CC=1Cl>[Pd]>[Cl:39][C:36]1[CH:37]=[CH:38][C:33]([C@@:13]23[O:32][C@@:10]([CH2:52][OH: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][CH2:48][CH:49]([F:51])[F:50])=[CH:43][CH:42]=1

Participants

4

Reactant 2

HCID 72391,2-DichlorobenzeneHCID 86685173[(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]methanol

Product 1

HCID 86685174(1S,2S,3S,4R,5S)-5-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triolYield 36%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

[(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]methanol 12m (76 mg, 0.10 mmol) was dissolved in 10 mL of mixed solution (THF and MeOH, v:v=1:1), followed by addition of o-dichlorobenzene (103 μL, 0.9 mmol) and Palladium/carbon (180 mg, 10%). The mixture was exchanged with H2 three times and stirred for 2 hours, then filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by column chromatography to obtain the title compound (1S,2S,3S,4R,5S)-5-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol 12 (17 mg, pale yellow solid), yield: 34.0%. MS m/z (ESI): 490.24 [M+18]; 1H NMR (400 MHz, CD3OD): δ 7.48-7.49 (m, 1H), 7.37-7.39 (m, 2H), 7.15-7.17 (d, 2H), 6.88-6.91 (d, 2H), 6.02-6.29 (ddt, 1H), 4.23-4.24 (d, 1H), 4.20-4.21 (d, 1H), 4.16-4.17 (d, 1H), 4.08 (s, 2H), 3.78-3.88 (m, 2H), 3.67-3.72 (m, 2H), 3.55-3.57 (m, 2H).

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customthe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-347202cf7aa64949be8c7501a4c6ac7c
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

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