Formaldehyde → 2,5-Anhydro-2-C-(hydroxymethyl)-3,4,6-tris-O-(phenylmethyl)-D-arabino-hexitol

HRID 1073449Notes

Reaction equation

HRID 1073449 reaction equation
[C:1]1([CH2:7][O:8][C@H:9]2[C@H:15]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C@@H:14]([CH2:24][O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[O:13][C@@H:10]2[CH:11]=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[C:35](=O)([O-])[O-:36].[K+].[K+]>CO>[OH:12][CH2:11][C:10]1([O:13][C@H:14]([CH2:24][O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C@@H:15]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C@@H:9]1[O:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:35][OH:36]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 108364862,5-anhydro-3,4,6-tris-O-(phenylmethyl)-D-mannose

Product 1

HCID 139625822,5-Anhydro-2-C-(hydroxymethyl)-3,4,6-tris-O-(phenylmethyl)-D-arabino-hexitol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In accordance with Flowchart F, 2,5-anhydro-3,4,6-tris-O-(phenylmethyl)-D-mannose 29 is reacted with formalin and potassium carbonate in methanol at about 85° C. under an inert atmosphere, then acidified, giving 2,5-anhydro-2-C-(hydroxymethyl)-3,4,6-tris-O-(phenylmethyl)-D-glucitol 42. which is reacted with borontrifluoride etherate in acetic anhydride at reduced temperature followed by treatment with sodium bicarbonate, giving 2-C-[(acetyloxy)methyl]-2,5-anhydro-3,4-bis-O-(phenylmethyl)-D-glucitol, 1,6-diacetate 43. Compound 43 is reacted with aqueous potassium carbonate in methanol at reflux, giving 2,5-anhydro-2-C-(hydroxymethyl)-3,4-bis-O-(phenylmethyl)-D-glucitol 44, which is reacted with benzaldehyde dimethyl acetal and p-toluenesulfonic acid in dimethylformamide at about 60° C. under reduced pressure, giving a mixture of [R] and [S]-2,5-anhydro-2-C-(hydroxymethyl)-3,4-bis-O-(phenylmethyl)-1,21 -O-(phenylmethylene)-D-glucitol 45 and 46. The mixture 45 and 46 is reacted with aluminum chloride and lithium aluminum hydride in ether/dichloromethane under an inert atmosphere, giving a mixture of 2,5-anhydro-2-C-[(phenylmethoxy)methyl]-3,4-bis-O-(phenylmethyl)-D-glucitol and 2,5-anhydro-2-C-(hydroxymethyl)-1,3,4 -tris-O-(phenylmethyl)-D-glucitol 47, which is reacted with diphenyl phosphorochloridate in pyridine at reduced temperature, giving a mixture of 2,5-anhydro-2-C-[(phenylmethoxy)methyl]-3,4-bis-O-(phenylmethyl)-D-glucitol, 1,6-bis (diphenyl phosphate) and 2,5-anhydro-2-C-[[(diphenoxyphosphinyl)oxy]methyl]-1, 3,4-tris-O-(phenylmethyl)-D-glucitol, 6-diphenyl phosphate 48. The mixture 48 is hydrogenated in methanol and acetic acid over palladium on carbon, giving, after chromatography, the product of Formula I where R', R", R'" and R"" are phenyl, 2,5-anhydro-2-C-(hydroxymethyl)-D-glucitol, 1,6-bis(diphenyl phosphate) 49. Substitution of other esterifying agents as described in Flowchart A will result in the corresponding tetraesters. Compound 49 may then be hydrogenated in methanol over platinum oxide, giving the product of Formula I where R', R", R'" and R"" are hydrogen, 2,5-anhydro-2-C-(hydroxymethyl)-D-glucitol, 1,6-bis(dihydrogen phosphate) 50. ##STR19##

Sources & evidence

ORD record
ord-989cb7a808734eb2b2f0b7ef14700b87
Source dataset
uspto-grants-1990_11
Patent number
US04968790

Reaction notes

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