Trityl chloride → HCID 69734797, compound

HRID 1815725Notes

Reaction equation

HRID 1815725 reaction equation
[CH2:1]([CH:4]1[CH:9]([OH:10])[CH:8]([OH:11])[CH:7]([OH:12])[CH:6]([CH2:13][OH:14])[O:5]1)[CH:2]=[CH2:3].[C:15](Cl)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(O[C:39](=[O:41])[CH3:40])(=O)C>N1C=CC=CC=1>[C:4]([O:11][CH:8]1[CH:9]([O:10][C:9](=[O:10])[CH3:8])[CH:4]([CH2:1][CH:2]=[CH2:3])[O:5][CH:6]([CH2:13][O:14][C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:7]1[O:12][C:39](=[O:41])[CH3:40])(=[O:5])[CH3:1]

Participants

5

Reactant 3

HCID 6456Trityl chlorideHCID 7918Acetic AnhydrideHCID 14259408HCID 14259408, compound

Product 1

HCID 69734797HCID 69734797, compoundYield 140.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
40 °C

Procedure

2-Allyl-6-hydroxymethyl-tetrahydropyran-3,4,5-triol (962 mg, 4.72 mmol) prepared by the method of Giannis and Sandhoff (Tetrahedron Letters, 1985, 26, 1479-1482; incorporated herein by reference) was dissolved in pyridine (10 ml). To this solution was added trityl chloride (2.6 g, 9.4 mmol) and the mixture stirred for 24 hours at 40° C. Acetic anhydride (2.0 ml, 21 mmol) was added and the mixture stirred for a further 18 hours whereupon it was poured into ice cold water (50 ml) and this was extracted with chloroform (3×50 ml). The combined chloroform extracts were washed with water (50 ml), dried (sodium sulfate), filtered and taken to dryness under reduced pressure. The residue was chromatographed on a silica gel (0.063-0.2 mm) column (2×40 cm), eluted with petroleum spirit (bp 60-80°): ethyl acetate (4:1) to give acetic acid 4,5-diacetoxy-6-allyl-2-trityloxymethyl-tetrahydropyran-3-yl ester (1.9 g, 70%). This compound (1.9 g, 3.32 mmol) and dry ferric chloride (1.2 g) were stirred at room temperature in dichloromethane (25 ml) for 2 hours. Water was added to the reaction mixture and this was extracted with chloroform (3×50 ml). The combined chloroform extracts were washed with water (50 ml), dried (sodium sulfate) filtered and evaporated to dryness under reduced pressure. The residue was chromatographed on a silica gel (0.063-0.2 mm) column (2×30 cm), eluted with petroleum spirit (bp 60-80°): ethyl acetate (1:1) to give acetic acid 4,5-diacetoxy-6-allyl-2-hydoxymethyl-tetrahydropyran-3-yl ester (900 mg, 82%). This compound (900 mg, 2.23 mmol) and pyridine (237 mg, 3.0 mmol) were dissolved in toluene (15 ml), to this solution under a nitrogen atmosphere at 0° C. was added phosphorus oxychloride (460 mg, 2.9 mmol) dropwise with stirring. After the addition the mixture was allowed to come to room temperature and stir for 2 hours. The reaction was filtered and evaporated to dryness under reduced pressure. The residue was dissolved in a 1:1 mixture of acetone (10 ml) and water (10 ml) and heated at 50 to 60° for 2 hours. The mixture was taken to dryness under reduced pressure and the residue evaporated once each from ethanol, methanol and acetone (25 ml) to give acetic acid 4,5-diacetoxy-6-allyl-2-phosphonooxymethyl-tetrahydro-pyran-3-yl ester (851 mg, 76%). This compound (851 mg, 2.08 mmol) was dissolved in methanol (10 ml) to this was added sodium methoxide (247 mg, 4.57 mmol) in methanol (5 ml) and the mixture stirred for 2 hours at room temperature. The mixture was taken to dryness under reduced pressure and the residue dissolved in water (10 ml) and treated with cation exchange resin (Dowex 50 H+ form) to remove sodium ions. After filtration the mixture was taken to dryness to give phosphoric acid mono-(6-allyl-3,4,5-trihydroxy-tetrahydro-pyran-2-ylmethyl) ester (580 mg, 98.5%). This compound (580 mg, 2.04 mmol) was dissolved in water (1.0 ml) and sodium acetate (168 mg, 2.05 mmol) in methanol (5 ml) was added. A further amount of water (1.0 ml) was added and the resulting mixture was added dropwise with stirring to ethanol (50 ml). The resulting precipitate was isolated by centrifugation to give phosphoric acid mono-(6-allyl-3,4,5-trihydroxy-tetrahydro-pyran-2-ylmethyl) ester mono sodium salt (480 mg, 76.3%), 1Hnmr (500 MHz, D2O): δ 2.16-2.30 (m, 1H), 2.34-2.48 (m, 1H), 3.46-3.54 (m, 1H) 3.62-3.94 (m, 6H), 4.95-5.08 (m, 2H), 5.62-5.76 (m, 1H); ESMS (−ve) 283 (M−H). This compound (284 mg, 1 mmol) was dissolved in methanol (25 ml) stirred under a hydrogen atmosphere in the presence of 10% palladium on charcoal until uptake of hydrogen ceased. The catalyst was removed by filtration and the filtrate taken to dryness under reduced pressure to give phosphoric acid mono-(6-propyl-3,4,5-trihydroxy-tetrahydro-pyran-2-ylmethyl) ester (quantitative). From this compound, in a similar manner to the allyl compound above, was prepared phosphoric acid mono-(6-propyl-3,4,5-trihydroxy-tetrahydro-pyran-2-ylmethyl) ester mono sodium salt (79%), ESMS (−ve) 285 (M−H).

Workup

  1. stirringthe mixture stirred for a further 18 hours whereupon it
  2. extractionthis was extracted with chloroform (3×50 ml)
  3. washThe combined chloroform extracts were washed with water (50 ml)
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customThe residue was chromatographed on a silica gel (0.063-0.2 mm) column (2×40 cm)
  7. washeluted with petroleum spirit (bp 60-80°)

Sources & evidence

ORD record
ord-da23ecfbdba24972a917f7ca6d14b16e
Source dataset
uspto-grants-2005_04
Patent number
US06878690B2

Reaction notes

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