Diisopropylethylamine → 2,5-anhydro-1-C-(diethoxyphosphinyl)-3,4,6-tris-O-(phenylmethyl)-1-O-[[2-(trimethylsilyl)ethoxy]methyl]-D-mannitol

HRID 2166288Notes

Reaction equation

HRID 2166288 reaction equation
C1(CO[C@H]2[C@H](OCC3C=CC=CC=3)[C@@H](COCC3C=CC=CC=3)O[C@@H]2C=O)C=CC=CC=1.P([O-])(OCC)OCC.[O-]CC.[Na+].[CH2:45]([O:47][P:48]([O:82][CH2:83][CH3:84])([CH:50]([OH:81])[C@@H:51]1[O:71][C@H:70]([CH2:72][O:73][CH2:74][C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)[C@@H:61]([O:62][CH2:63][C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[C@@H:52]1[O:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:49])[CH3:46].C(N(CC)C(C)C)(C)C.[CH3:94][Si:95]([CH3:102])([CH3:101])[CH2:96][CH2:97][O:98][CH2:99]Cl>ClCCl>[CH2:45]([O:47][P:48]([O:82][CH2:83][CH3:84])([CH:50]([O:81][CH2:99][O:98][CH2:97][CH2:96][Si:95]([CH3:102])([CH3:101])[CH3:94])[C@H:51]1[O:71][C@H:70]([CH2:72][O:73][CH2:74][C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)[C@@H:61]([O:62][CH2:63][C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[C@@H:52]1[O:53][CH2:54][C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)=[O:49])[CH3:46]

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 2723922Sodium ethoxideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 3780918DiethylphosphiteHCID 108364862,5-anhydro-3,4,6-tris-O-(phenylmethyl)-D-mannoseHCID 1317164822,5-anhydro-1-C-(diethoxyphosphinyl)-3,4,6-tris-O-(phenylmethyl)-D-glucitol

Product 1

HCID 1317164812,5-anhydro-1-C-(diethoxyphosphinyl)-3,4,6-tris-O-(phenylmethyl)-1-O-[[2-(trimethylsilyl)ethoxy]methyl]-D-mannitol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In accordance with Flowchart C, 2,5-anhydro-3,4,6-tris-O-(phenylmethyl)-D-mannose 4 is reacted with diethyl phosphite and sodium ethoxide under argon, giving [lR(and/or IS)]-2,5-anhydro-1-C-(diethoxyphosphinyl)-3,4,6-tris-O-(phenylmethyl)-D-glucitol 21, which is reacted with N,N-diisopropylethylamine and 2-(trimethylsilyl)ethoxymethyl chloride in dry dichloromethane under argon at reflux, giving [1R-(and/or 1S)]-2,5-anhydro-1-C-(diethoxyphosphinyl)-3,4,6-tris-O-(phenylmethyl)-1-O-[[2-(trimethylsilyl)ethoxy]methyl]-D-mannitol 22. Compound 22 is hydrogenated in methanol over palladium hydroxide on carbon, giving [lR(and/or lS)]-2,5-anhydro-1-C-(diethoxyphosphi8nyl)-1-O-[[2-(trimethylsilyl)ethoxy]methyl]-D-mannitol 23 which is then reacted with diphenyl chlorophosphate in pyridine at ice bath temperature, giving [1R(and/or 1S)]-2,5-anhydro-1-C-(diethoxyphosphinyl)-1-0-[[2-(trimethylsilyl)ethoxy]methyl]-D-mannitol, 6-(diphenyl phosphate) 24. Compound 24 is reacted with boron trifluoride etherate in anhydrous acetonitrile under argon, giving [1R(and/or 1S)]-2,5-anhydro-1-C-(diethoxyphosphinyl)-D-mannitol, 6-(diphenyl phosphate) 25 which is then reacted with bromotrimethylsilane in deuterated chloroform under argon, giving [1R(and/or 1S)]-2,5-anhydro-1-C-phosphono-D-mannitol, 6-(diphenyl phosphate) 26 which is hydrogenated in methanol over platinum oxide, giving [1R(and/or 1S)]-2,5-anhydro-1-C-phosphono-D-mannitol, 6-(dihydrogen phosphate) 27. ##STR12##

Workup

  1. customgiving [lR(and/
  2. temperatureat reflux

Sources & evidence

ORD record
ord-f13ad3bf8bb044c3bdd3ce38ff16f72f
Source dataset
uspto-grants-1990_07
Patent number
US04943629

Reaction notes

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