1,2-Dichlorobenzene → (1R,2S,3S,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-7-methyl-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol

HRID 1055517Notes

Reaction equation

HRID 1055517 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][CH3:49])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH2:51][OH:52])[CH:11]([CH3:50])[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]([CH2:51][OH:52])([CH:11]([CH3:50])[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][CH3:49])=[CH:43][CH:42]=1

Participants

5

Reactant 2

HCID 72391,2-DichlorobenzeneHCID 131736384[(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-7-methyl-6,8-dioxabicyclo[3.2.1]octan-1-yl]methanol

Product 1

HCID 117986004(1R,2S,3S,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-7-methyl-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triolYield 58.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of [(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-7-methyl-6,8-dioxabicyclo[3.2.1]octan-1-yl]methanol 8c (258 mg, 0.37 mmol) in a methanol/tetrahydrofuran mixture (v/v=4/1, 15 mL) were added o-dichlorobenzene (0.21 mL, 1.82 mmol) and 10% Pd/C (19.3 mg, 0.18 mmol) in turn. The mixture was stirred at room temperature under H2 for 4.5 hours and filtered. The filter cake was washed with a methanol/tetrahydrofuran mixture (v/v=4/1, 10 mL×2). The combined filtrates were concentrated in vacuo. The residue was purified by prep-HPLC to give the title compound 8 as white powder (98 mg, 59%, HPLC: 97.2%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 451.1[M+H]+; and 1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.43-7.36 (m, 2H), 7.30 (d, 1H), 7.09 (d, 2H), 6.82 (d, 2H), 5.15 (d, 1H), 4.99 (d, 1H), 4.92 (d, 1H), 4.74 (t, 1H), 3.96 (m, 5H), 3.76 (dd, 1H), 3.62 (m, 2H), 3.51 (dd, 1H), 3.40 (d, 1H), 1.36 (d, 3H), 1.29 (t, 3H).

Workup

  1. filtrationfiltered
  2. washThe filter cake was washed with a methanol/tetrahydrofuran mixture (v/v=4/1, 10 mL×2)
  3. concentrationThe combined filtrates were concentrated in vacuo
  4. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-7004e8ded8be40dfa7108e13586eb31a
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

Loading…