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

HRID 1055558Notes

Reaction equation

HRID 1055558 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]([F:52])([F:51])[F:50])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([C:53]([OH:55])=[O:54])[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:61](=O)(O)[O-].[Na+]>CO>[CH3:61][O:54][C:53]([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][CH2:48][C:49]([F:51])([F:50])[F:52])=[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:55]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 118377789(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoro ethoxy)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylic acid

Product 1

HCID 118377811methyl(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoro ethoxy)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylateYield 81.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoroethoxyl)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylic acid 18a (0.74 g, 0.95 mmol) in methanol (40 mL) was added concentrated sulphuric acid (0.75 mL, 13.8 mmol) at 0° C. The mixture was warmed up to room temperature and stirred for 12 hours, and then adjusted with saturated aqueous sodium bicarbonate to pH 8 and concentrated in vacuo to remove most of the solvent. To the residue was added water (50 mL). The resulting mixture was extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (80 mL), dried over anhydrous sodium sulfate and filtrated. The filtrate was concentrated in vacuo to give the title compound 18b as orange-yellow oil (0.6 g, 81.1%). This material was not further purified. The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, CDCl3) δ(ppm): 7.45 (d, 1H), 7.41-7.35 (m, 2H), 7.34-7.27 (m, 6H), 7.24 (m, 4H), 7.20 (t, 1H), 7.15 (t, 2H), 7.08 (d, 2H), 6.85 (d, 2H), 6.76 (d, 2H), 4.82 (m, 2H), 4.77 (d, 1H), 4.61 (d, 1H), 4.51 (d, 1H), 4.25 (m, 3H), 4.17 (t, 2H), 4.07 (d, 1H), 3.99 (m, 2H), 3.84 (d, 1H), 3.72 (d, 1H), 3.69 (s, 3H).

Workup

  1. concentrationconcentrated in vacuo
  2. customto remove most of the solvent
  3. additionTo the residue was added water (50 mL)
  4. extractionThe resulting mixture was extracted with ethyl acetate (50 mL×3)
  5. washThe combined organic layers were washed with saturated aqueous sodium chloride (80 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltrated
  8. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-2814d5b499c84dcb87e3be56e0c5f549
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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