p-Toluenesulfonic acid → [(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

HRID 1055516Notes

Reaction equation

HRID 1055516 reaction equation
C([O:8][C@H:9]1[C@H:14]([O:15][CH2:16]C2C=CC=CC=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@:12]([C:33]2[CH:38]=[CH:37]C(Cl)=[C:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[CH:43][CH:42]=3)[CH:34]=2)(OC)[O:11][C@:10]1([CH:52]([OH:54])[CH3:53])[CH2:50][OH:51])C1C=CC=CC=1.[C:55]1([CH3:65])[CH:60]=[CH:59][C:58](S(O)(=O)=O)=[CH:57][CH:56]=1.Cl[CH2:67][Cl:68]>>[CH2:65]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@:12]2([C:33]3[CH:38]=[CH:37][C:67]([Cl:68])=[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:11][C@@:10]1([CH2:50][OH:51])[CH:52]([CH3:53])[O:54]2)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

Participants

4

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 6344DichloromethaneHCID 118377802HCID 118377802, compound

Product 1

HCID 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]methanolYield 44.8%

Procedure

To a solution of 1-[(2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]ethanol 8b (0.6 g, 0.80 mmol) in dichloromethane (20 mL) was added p-toluenesulfonic acid (27.5 mg, 0.16 mmol). The mixture was stirred at room temperature for 2 hours and quenched with 5 mL of saturated aqueous sodium bicarbonate. The resulting mixture was partitioned. The aqueous layer was extracted with dichloromethane (10 mL×2). The combined organic layers were washed with water (10 mL×2) and then saturated aqueous sodium chloride (10 mL×2), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=10/1 to give the title compound 8c as coloeless oil (258 mg, 44.8%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ (ppm): 7.41 (s, 1H), 7.34 (m, 4H), 7.31-7.27 (m, 6H), 7.24 (m, 2H), 7.14 (m, 3H), 7.06 (d, 2H), 6.89-6.83 (m, 2H), 6.77-6.72 (m, 2H), 4.86 (m, 3H), 4.74 (d, 1H), 4.32 (dd, 1H), 4.23 (d, 1H), 4.08 (m, 1H), 4.05-3.98 (m, 3H), 3.98-3.89 (m, 3H), 3.77 (d, 1H), 3.68 (d, 1H), 3.64 (d, 1H), 1.56 (d, 3H), 1.38 (t, 3H).

Workup

  1. customquenched with 5 mL of saturated aqueous sodium bicarbonate
  2. customThe resulting mixture was partitioned
  3. extractionThe aqueous layer was extracted with dichloromethane (10 mL×2)
  4. washThe combined organic layers were washed with water (10 mL×2)
  5. dry with materialsaturated aqueous sodium chloride (10 mL×2), dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluted with PE/EtOAc(v/v)=10/1

Sources & evidence

ORD record
ord-3e25d56974864e0db7a76422931e5595
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

Loading…