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

HRID 1055544Notes

Reaction equation

HRID 1055544 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][C:48]([F:51])([F:50])[F:49])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([C:52]([OH:54])=[O:53])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.S(=O)(=O)(O)O.[C:62](=O)(O)[O-].[Na+]>O1CCCC1>[CH3:62][O:53][C:52]([C@:10]12[O:32][C@:13]([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][C:48]([F:49])([F:50])[F:51])=[CH:43][CH:42]=4)[CH:34]=3)([O:12][CH2:11]1)[C@H:14]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@@H:15]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@@H:9]2[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:54]

Participants

6

Reactant 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 118377838(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylic acid

Product 1

HCID 118377839methyl(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(trifluoro methoxy)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylateYield 66.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylic acid 16a (0.49 g, 0.64 mmol) in tetrahydrofuran (2 mL) were added methanol (8 mL) and concentrated sulphuric acid (0.24 mL) at room temperature. The mixture was stirred at 45° C. for 20 hours. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate till pH becomes 7 and extracted with ethyl acetate (10 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (10 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)=20/1 to give the title compound 16b as a white solid (322 mg, 66.5%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.48 (d, 1H), 7.44-7.38 (m, 2H), 7.32 (m, 7H), 7.26 (m, 3H), 7.21 (d, 1H), 7.16 (m, 4H), 7.05 (d, 2H), 6.87 (d, 2H), 4.90-4.81 (m, 2H), 4.79 (d, 1H), 4.63 (d, 1H), 4.53 (d, 1H), 4.32 (d, 1H), 4.20 (dd, 2H), 4.10 (t, 2H), 4.02 (dd, 1H), 3.89 (d, 1H), 3.74 (d, 1H), 3.71 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (10 mL×3)
  2. washThe combined organic layers were washed with saturated aqueous sodium chloride (10 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)=20/1

Sources & evidence

ORD record
ord-24aba18a70f1467b9cf6ccab818b31bb
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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