Potassium Phosphate, Tribasic → methyl 2-[2(3-[(2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]phenyl)ethyl]azulene-1-carboxylate

HRID 1375999Notes

Reaction equation

HRID 1375999 reaction equation
C12BC(CCC1)CCC2.[CH2:10]([O:17][C@@H:18]1[C@@H:23]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@H:22]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@@H:21]([CH2:40][O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[O:20][C@H:19]1[C:49]1[CH:54]=[CH:53][CH:52]=[C:51]([CH:55]=[CH2:56])[CH:50]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[C:66]1[CH:75]=[C:74]2[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=[CH:73]2)[C:67]=1[C:76]([O:78][CH3:79])=[O:77]>Cl[Pd]Cl.C1(P[C-]2C=CC=C2)C=CC=CC=1.[C-]1(PC2C=CC=CC=2)C=CC=C1.[Fe+2].O.CN(C=O)C.C1COCC1>[CH2:10]([O:17][C@@H:18]1[C@@H:23]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@H:22]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@@H:21]([CH2:40][O:41][CH2:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[O:20][C@H:19]1[C:49]1[CH:50]=[C:51]([CH2:55][CH2:56][C:66]2[CH:75]=[C:74]3[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=[CH:73]3)[C:67]=2[C:76]([O:78][CH3:79])=[O:77])[CH:52]=[CH:53][CH:54]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 789669-Borabicyclo(3.3.1)nonaneHCID 22107186Methyl 2-chloroazulene-1-carboxylateHCID 58786238(1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-(3-vinylphenyl)-D-glucitol

Product 1

HCID 58786187methyl 2-[2(3-[(2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]phenyl)ethyl]azulene-1-carboxylateYield 68.2%

Reagents, catalysts & solvents 4

HCID 1784797941,1'-diphenylphosphinoferrocene dichloropalladium (II)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A THF solution (8.0 ml) of 9-borabicyclo[3.3.1]nonane was added to (1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-(3-vinylphenyl)-D-glucitol (1.0 g) and the mixture was refluxed with heating for four hours. Next, a 3 M aqueous solution of potassium phosphate (1.3 ml) and DMF (12 ml) were added to the reaction mixture. Methyl 2-chloroazulene-1-carboxylate (0.35 g) and 1,1′-diphenylphosphinoferrocene dichloropalladium (II) (0.12 g) were further added to the mixture, followed by stirring at 50° C. for two hours. After cooling to room temperature, the reaction mixture was poured into ice-cooled water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium hydrogencarbonate and saturated brine in that order and dried over anhydrous sodium sulfate. The reaction mixture was concentrated. The residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain methyl 2-[2(3-[(2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]phenyl)ethyl]azulene-1-carboxylate (0.88 g).

Workup

  1. temperaturethe mixture was refluxed
  2. temperaturewith heating for four hours
  3. temperatureAfter cooling to room temperature
  4. additionthe reaction mixture was poured into ice-
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with saturated aqueous solution of sodium hydrogencarbonate and saturated brine in that order
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationThe reaction mixture was concentrated
  9. customThe residue was purified by silica gel column chromatography (n-hexane-ethyl acetate)

Sources & evidence

ORD record
ord-d12ab9dd791f4990945ccb0b6dfacdee
Source dataset
uspto-grants-2007_01
Patent number
US07169761B2

Reaction notes

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