Sulfuric Acid → methyl (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylate

HRID 1055605Notes

Reaction equation

HRID 1055605 reaction equation
[CH2:1]([O:8][C@H:9]1[C@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=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][C:49]5[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=5)=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([C:55]([OH:57])=[O:56])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[C:63](=O)(O)[O-].[Na+]>CO.O1CCCC1>[CH2:1]([O:8][C@H:9]1[C@H:15]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=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][C:49]5[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=5)=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([C:55]([O:57][CH3:63])=[O:56])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 118377825(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylic acid

Product 1

HCID 131736401methyl (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylateYield 84.4%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylic acid 25m (0.45 g, 0.57 mmol) in a methanol/tetrahydrofuran mixture (v/v=6/5, 22 mL) was added concentrated sulphuric acid (0.05 mL) at room temperature. The mixture was warmed up to 60° C. and stirred for 14 hours. The reaction mixture was adjusted with saturated aqueous sodium bicarbonate to pH 7 at room temperature and extracted with ethyl acetate (60 mL). The organic layer was washed with saturated brine (20 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)=6/1 to give the title compound 25n as a pale yellow solid (0.38 g, 84.4%). The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, CDCl3) δ(ppm): 7.48 (m, 1H), 7.47 (m, 2H), 7.41 (m, 4H), 7.33 (m, 7H), 7.25 (m, 3H), 7.21 (m, 4H), 7.16 (m, 2H), 7.08 (m, 2H), 6.87 (m, 2H), 5.01 (s, 2H), 4.81-4.75 (m, 3H), 4.78 (m, 1H), 4.63 (d, 1H), 4.52 (d, 1H), 4.26 (d, 1H), 4.19 (m, 2H), 4.09 (m, 1H), 4.01 (m, 2H), 3.87 (m, 1H), 3.74 (d, 1H), 3.71 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (60 mL)
  2. washThe organic layer was washed with saturated brine (20 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)=6/1

Sources & evidence

ORD record
ord-62754da7c7a44e30b2b1522d591a59ab
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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