Methanol → HCID 131736386, compound

HRID 1055564Notes

Reaction equation

HRID 1055564 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][CH3:49])=[C:43]([F:50])[CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([C:51]([OH:53])=[O:52])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[CH3:59]O>>[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:27]=[CH:28][CH:29]=[CH:30][CH:31]=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][CH3:49])=[C:43]([F:50])[CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([C:51]([O:53][CH3:59])=[O:52])[CH2:11][O:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 118377790HCID 118377790, compound

Product 1

HCID 131736386HCID 131736386, compoundYield 46.2%

Procedure

To a solution of (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxy-3-fluoro-phenyl)methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylic acid 20b (1.20 g, 1.38 mmol) in methanol (30 mL) was added concentrated sulphuric acid (150 mg, 1.53 mmol) at room temperature. The mixture was stirred at room temperature for 12 hours and then 40° C. for 6 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate (3 mL) at 0° C. and concentrated in vacuo to remove most of the solvent. To the residue was added water (20 mL). The resulting mixture was extracted with ethyl acetate (20 mL). The combined organic layers were washed with saturated brine (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)=1/1 to give the title compound 20c as colorless semi-solid (0.48 g, 46.2%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.43 (d, 1H), 7.36 (p, 2H), 7.27 (m, 10H), 7.15 (m, 3H), 6.86 (dd, 3H), 6.78 (m, 2H), 4.82 (q, 2H), 4.75 (d, 1H), 4.60 (d, 1H), 4.50 (d, 1H), 4.26 (d, 1H), 4.17 (dd, 2H), 4.00 (m, 5H), 3.85 (d, 1H), 3.71 (d, 1H), 3.68 (s, 3H), 1.40 (t, 3H).

Workup

  1. wait40° C. for 6 hours
  2. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate (3 mL) at 0° C.
  3. concentrationconcentrated in vacuo
  4. customto remove most of the solvent
  5. additionTo the residue was added water (20 mL)
  6. extractionThe resulting mixture was extracted with ethyl acetate (20 mL)
  7. washThe combined organic layers were washed with saturated brine (10 mL×2)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customthe residue was purified by silica gel chromatography
  12. washeluted with PE/EtOAc(v/v)=1/1

Sources & evidence

ORD record
ord-c0a9a611ed0d4cc2a0fe5c239e67690e
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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