Cesium carbonate → HCID 57414008, compound

HRID 1428974Notes

Reaction equation

HRID 1428974 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](B3OC(C)(C)C(C)(C)O3)=[CH:23][CH:22]=2)[C@H:6]1CC([O-])=O)(=O)C.Br[C:41]1[CH:42]=[N:43][CH:44]=[C:45]([CH:50]=1)[C:46]([O:48][CH3:49])=[O:47].C(=O)([O-])[O-:52].[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>[OH:52][C@H:6]1[C@@H:5]([OH:4])[C@H:10]([OH:11])[C@@H:9]([CH2:15][OH:16])[O:8][C@@H:7]1[O:20][C:21]1[CH:22]=[CH:23][C:24]([C:41]2[CH:50]=[C:45]([C:46]([O:48][CH3:49])=[O:47])[CH:44]=[N:43][CH:42]=2)=[CH:25][CH:26]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 699336Methyl 5-bromopyridine-3-carboxylateHCID 86674311HCID 86674311, compound

Product 1

HCID 57414008HCID 57414008, compoundYield 40%

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-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]tetrahydropyran-3-yl]acetate (0.132 g, 0.24 mmol), methyl 5-bromonicotinate (0.043 g, 0.2 mmol), cesium carbonate (0.196 g, 0.6 mmol) and tetrakis(triphenylphosphine)palladium (0.023 g, 0.02 mmol) in dioxane/water (5 mL/1 mL) was heated at 80° C. with stirring for 1 h. After cooling down, the mixture was filtered through silica gel column to remove the metal catalyst and salts with hexane/ethyl acetate (2/1) containing 2% triethylamine as eluent. The filtrate was concentrated, then dried in vacuo. Into the residue, 6 mL of methanol with catalytic amount of sodium methoxide (0.02 M) was added and the mixture was stirred at room temperature overnight. The solvent was removed. The resulting residue was purified by silica gel chromography with CH2Cl2/MeOH combinations containing 2% NH3/H2O as eluent, giving rise to 12b (0.031 g) in 40% yield. 1H NMR (300 MHz, CD3OD) δ ppm 3.53-3.65 (m, 1H) 3.67-3.83 (m, 3H) 3.89-3.96 (m, 1H) 3.99 (s, 3H) 4.04 (dd, J=3.43, 1.79 Hz, 1H) 5.57 (d, J=1.92 Hz, 1H) 7.22-7.37 (m, 2H) 7.58-7.73 (m, 2H) 8.54 (t, J=2.06 Hz, 1H) 8.97 (d, J=2.20 Hz, 1H) 9.04 (d, J=1.92 Hz, 1H). MS (ESI): found: [M+H]+, 392.1.

Workup

  1. temperatureAfter cooling down
  2. filtrationthe mixture was filtered through silica gel column
  3. customto remove the metal catalyst and salts with hexane/ethyl acetate (2/1)
  4. additioncontaining 2% triethylamine as eluent
  5. concentrationThe filtrate was concentrated
  6. customdried in vacuo
  7. additionInto the residue, 6 mL of methanol with catalytic amount of sodium methoxide (0.02 M) was added
  8. stirringthe mixture was stirred at room temperature overnight
  9. customThe solvent was removed
  10. customThe resulting residue was purified by silica gel chromography with CH2Cl2/MeOH combinations
  11. additioncontaining 2% NH3/H2O as eluent

Sources & evidence

ORD record
ord-0514649b908348fd8882aec3c9b8952b
Source dataset
uspto-grants-2015_01
Patent number
US08937167B2

Reaction notes

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