p-Toluenesulfonic acid monohydrate → (1S,2S,3S,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-2-ol

HRID 1055612Notes

Reaction equation

HRID 1055612 reaction equation
[CH2:1]([O:8][C@H:9]1[C@:15]2([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH2:24][C:25]4[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH3:33])=[CH:27][CH:26]=4)[CH:18]=3)[O:16][C@@:12]3([CH2:34][O:35]C(C4C=CC=CC=4)[O:37][C@H:11]3[C@@H:10]1[O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[CH2:13][O:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Na]>C(#N)C>[CH2:45]([O:44][C@@H:10]1[C@@H:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C@:15]2([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH2:24][C:25]4[CH:26]=[CH:27][C:28]([O:31][CH2:32][CH3:33])=[CH:29][CH:30]=4)[CH:18]=3)[O:16][C@@:12]([CH2:34][OH:35])([CH2:13][O:14]2)[C@H:11]1[OH:37])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 5360545SodiumHCID 118391147(4aS,7S,8R,9S,9aS)-8,9-bis(benzyloxy)-7-(4-chloro-3-(4-ethoxybenzyl)phenyl)-2-phenylhexahydro-4a,7-epoxy[1,3]dioxino[5,4-c]oxepine

Product 1

HCID 118391141(1S,2S,3S,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-2-olYield 76%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (4aS,7S,8R,9S,9aS)-8,9-bis(benzyloxy)-7-(4-chloro-3-(4-ethoxybenzyephenye-2-phenylhexahydro-4a,7-epoxy[1,3]dioxino[5,4-c]oxepine 28c (17.56 g, 27.3 mmol) in acetonitrile (40 mL) was added p-toluenesulfonic acid monohydrate (9.4 g, 54.6 mmol) at room temperature. The mixture was stirred at room temperature for 12 hours and adjusted with saturated aqueous sodium bicarnonate till pH becomes 7. The resulting mixture was extracted with ethyl actate (100 mL×3). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2), dried over anhydrous sodium sulfate 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 the title compound 28d as a yellow solid (11.68 g, 76.0%). The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, CDCl3) δ (ppm): 7.35 (d, 1H), 7.29-7.26 (m, 4H), 7.24 (d, 3H), 7.11 (m, 3H), 6.99 (d, 2H), 6.82 (d, 2H), 6.67 (d, 2H), 4.79 (d, 1H), 4.62 (d, 1H), 4.15 (m, 2H), 3.99 (d, 1H), 3.90 (m, 4H), 3.76 (m, 4H), 3.57 (d, 2H), 1.31 (t, 3H).

Workup

  1. extractionThe resulting mixture was extracted with ethyl actate (100 mL×3)
  2. washThe combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by silica gel chromatography
  7. washeluted with PE/EtOAc(v/v)=3/1

Sources & evidence

ORD record
ord-1f2de945c9db4ef79f21ac5945d82958
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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