Potassium Phosphate, Tribasic → HCID 67115857, compound

HRID 1258853Notes

Reaction equation

HRID 1258853 reaction equation
[C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[CH:8]([C:19]2[CH:24]=[CH:23][C:22](Br)=[C:21]([CH2:26][C:27]3[CH:36]=[CH:35][C:30]4[O:31][CH2:32][CH2:33][O:34][C:29]=4[CH:28]=3)[CH:20]=2)[O:7][C@@H:6]1[CH2:37][O:38][C:39](=[O:41])[CH3:40])(=[O:3])[CH3:2].C1(P([CH:55]2[CH2:60][CH2:59]CCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(B(O)O)CC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[CH:8]([C:19]2[CH:24]=[CH:23][C:22]([CH:59]3[CH2:60][CH2:55]3)=[C:21]([CH2:26][C:27]3[CH:36]=[CH:35][C:30]4[O:31][CH2:32][CH2:33][O:34][C:29]=4[CH:28]=3)[CH:20]=2)[O:7][C@@H:6]1[CH2:37][O:38][C:39](=[O:41])[CH3:40])(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 67115778HCID 67115778, compound

Product 1

HCID 67115857HCID 67115857, compoundYield 193.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of acetic acid (2R,3R,4R,5S)-3,4,5-triacetoxy-6-[4-bromo-3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-phenyl]-tetrahydro-pyran-2-ylmethyl ester (10.0 g, 15.74 mmol) in toluene (100 mL) was added tricyclohexylphosphine (1.76 g, 6.29 mmol), a solution of potassium phosphate tribasic (13.3 g, 62.9 mmol) in water (15 mL), and cyclopropylboronic acid (4.06 g, 47.2 mmol). The reaction mixture was degassed for 45 min then palladium (II) acetate (529 mg, 2.3 mmol) was added. The reaction mixture was stirred at 90° C. overnight then cooled to room temperature and filtered through celite, and the celite was washed with ethyl acetate (200 mL). The organic layer of the filtrate was separated and washed with water (100 mL) followed by brine (100 mL), then dried over sodium sulfate and concentrated to give crude product which was further purified by column chromatography to furnish acetic acid (2R,3R,4R,5S)-3,4,5-triacetoxy-6-[4-cyclopropyl-3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-phenyl]-tetrahydro-pyran-2-ylmethyl ester (7.25 g, purity 98%) and this was recrystallized by absolute ethanol to give white solid (5.25 g, purity>99%).

Workup

  1. customThe reaction mixture was degassed for 45 min
  2. temperaturethen cooled to room temperature
  3. filtrationfiltered through celite
  4. washthe celite was washed with ethyl acetate (200 mL)
  5. customThe organic layer of the filtrate was separated
  6. washwashed with water (100 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customto give crude product which
  10. customwas further purified by column chromatography

Sources & evidence

ORD record
ord-52352d316f9e436db564f76de8f1dffe
Source dataset
uspto-grants-2013_06
Patent number
US08466114B2

Reaction notes

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