Cesium carbonate → HCID 57413864, compound

HRID 1428967Notes

Reaction equation

HRID 1428967 reaction equation
C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@@H:9]([CH2:15][O:16]C(=O)C)[O:8][C@H:7]([O:20][C:21]2[CH:26]=[CH:25][C:24](Br)=[CH:23][C:22]=2[CH3:28])[C@H:6]1CC([O-])=O)(=O)C.[CH3:33][NH:34][C:35]([C:37]1[CH:38]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:40]=[CH:41][CH:42]=1)=[O:36].C(=O)([O-])[O-:53].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:33][NH:34][C:35](=[O:36])[C:37]1[CH:38]=[CH:39][CH:40]=[C:41]([C:24]2[CH:25]=[CH:26][C:21]([O:20][C@@H:7]3[C@@H:6]([OH:53])[C@@H:5]([OH:4])[C@H:10]([OH:11])[C@@H:9]([CH2:15][OH:16])[O:8]3)=[C:22]([CH3:28])[CH:23]=2)[CH:42]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 53217108N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 86674309HCID 86674309, compound

Product 1

HCID 57413864HCID 57413864, compoundYield 64.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

Under nitrogen atmosphere, the mixture of [(2R,3S,4S,5R,6R)-4,5-diacetoxy-6-(acetoxymethyl)-2-(4-bromo-2-methyl-phenoxy)tetrahydropyran-3-yl]acetate (0.517 g, 1 mmol), 3-(N-methylaminocarbonyl)phenylboronic acid pinacol ester (0.392 g, 1.5 mmol), cesium carbonate (0.977 g, 3 mmol) and tetrakis(triphenylphosphine)palladium (0.116 g, 0.1 mmol) in dioxane/water (15 mL/3 mL) was heated at 80° C. with stirring for 1 h under a nitrogen atmosphere. After cooling to RT, the mixture was filtered through silica gel column to remove the metal catalyst and salts with hexane/ethyl acetate combinations as eluent. The filtrate was concentrated, and then dried in vacuo. The residue was diluted with 15 mL of methanol containing a catalytic amount of sodium methoxide (0.02 M) and the mixture was stirred at RT overnight. H+ exchange resin (DOWEX 50WX4-100) was added to neutralize the mixture. The resin was filtered off and the filtrate was concentrated. The resulting residue was purified by silica gel chromatography with CH2Cl2/MeOH combinations as eluent, giving the title compound (0.260 g) in 64% yield for two steps. 1H NMR (300 MHz, METHANOL-d4) δ ppm 7.94 (t, J=1.65 Hz, 1H), 7.57-7.72 (m, 2H), 7.33-7.50 (m, 3H), 7.23 (d, J=8.52 Hz, 1H), 5.48 (d, J=1.92 Hz, 1H), 4.00 (dd, J=1.79, 3.43 Hz, 1H), 3.83-3.94 (m, 1H), 3.60-3.76 (m, 3H), 3.46-3.58 (m, 1H), 2.87 (s, 3H), 2.24 (s, 3H). MS (ESI): found: [M+H]+, 404.2.

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe mixture was filtered through silica gel column
  3. customto remove the metal catalyst and salts with hexane/ethyl acetate combinations as eluent
  4. concentrationThe filtrate was concentrated
  5. customdried in vacuo
  6. additionThe residue was diluted with 15 mL of methanol containing a catalytic amount of sodium methoxide (0.02 M)
  7. stirringthe mixture was stirred at RT overnight
  8. additionH+ exchange resin (DOWEX 50WX4-100) was added
  9. filtrationThe resin was filtered off
  10. concentrationthe filtrate was concentrated
  11. customThe resulting residue was purified by silica gel chromatography with CH2Cl2/MeOH combinations as eluent

Sources & evidence

ORD record
ord-b3a77fe186b74547915aa59d705d120f
Source dataset
uspto-grants-2015_01
Patent number
US08937167B2

Reaction notes

Loading…