Potassium Phosphate, Tribasic → (2R,3R,4R,5S,6S)-2-(Acetoxymethyl)-6-(5-(4-ethylbenzyl)-4'-methoxy-6-methylbiphenyl-3-yl)-tetrahydro-2H-pyran-3,4,5-triyl triacetate

HRID 2206743Notes

Reaction equation

HRID 2206743 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])[C@H:8]([C:19]2[CH:24]=[C:23]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([CH2:32][CH3:33])=[CH:28][CH:27]=3)[C:22]([CH3:34])=[C:21](Br)[CH:20]=2)[O:7][C@@H:6]1[CH2:36][O:37][C:38](=[O:40])[CH3:39])(=[O:3])[CH3:2].[CH3:41][O:42][C:43]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=1.F[B-](F)(F)F.C1([PH+](C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[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])[C@H:8]([C:19]2[CH:20]=[C:21]([C:46]3[CH:47]=[CH:48][C:43]([O:42][CH3:41])=[CH:44][CH:45]=3)[C:22]([CH3:34])=[C:23]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([CH2:32][CH3:33])=[CH:28][CH:27]=3)[CH:24]=2)[O:7][C@@H:6]1[CH2:36][O:37][C:38](=[O:40])[CH3:39])(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 201262(4-Methoxyphenyl)boronic acidHCID 11710396Tricyclohexylphosphonium TetrafluoroborateHCID 59238239(2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(3-bromo-5-(4-ethylbenzyl)-4-methylphenyl)-tetrahydro-2H-pyran-3,4,5-triyl triacetate

Product 1

HCID 71110869(2R,3R,4R,5S,6S)-2-(Acetoxymethyl)-6-(5-(4-ethylbenzyl)-4'-methoxy-6-methylbiphenyl-3-yl)-tetrahydro-2H-pyran-3,4,5-triyl triacetateYield 93%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(3-bromo-5-(4-ethylbenzyl)-4-methylphenyl)-tetrahydro-2H-pyran-3,4,5-triyl triacetate (131) (WO2008/101939, Example V) (500 mg, 0.807 mmole) in toluene (6 mL) and water (3 mL) were added 4-methoxyphenylboronic acid (147 mg, 0.969 mmole), Pd(OAc)2 (18.1 mg, 0.0807 mmole), tricyclohexylphosphonium tetrafluoroborate (59.4 mg, 0.161 mmole), and K3PO4 (685 mg, 3.23 mmole). The mixture was stirred at 100° C. overnight. After cooling to ambient temperature, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by silica gel chromatography to yield the title compound (484 mg, 0.748 mmole, 93%) as a yellow solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-81f12fd58bc34f1e8850f82a60829e79
Source dataset
uspto-grants-2016_06
Patent number
US09371303B2

Reaction notes

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