Cesium carbonate → HCID 66721009, compound

HRID 1040347Notes

Reaction equation

HRID 1040347 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][C:17]=2OS(C(F)(F)F)(=O)=O)[CH:12]=[CH:13][C:14]=1[Cl:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:34]1[CH2:38][CH2:37][CH2:36][C:35]1=[O:39].C(=O)([O-])[O-].[Cs+].[Cs+].[NH4+].[Cl-]>O1CCOCC1.CCOCC.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][C:17]=2[N:34]2[CH2:38][CH2:37][CH2:36][C:35]2=[O:39])[CH:12]=[CH:13][C:14]=1[Cl:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 25517Ammonium ChlorideHCID 86637361HCID 86637361, compound

Product 1

HCID 66721009HCID 66721009, compoundYield 67.1%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
70 °C

Procedure

Stir a solution of 500 mg (1 mmol) of methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-{[(trifluoromethyl)sulphonyl]oxy}pyridine-2-carboxylate, 0.1 mL (1.1 mmol) of 2-pyrrolidinone and 450 mg (1.4 mmol) of caesium carbonate in 10 mL of anhydrous 1,4-dioxan for 10 minutes while bubbling with argon, then add 9 mg (0.01 mmol) of Pd2(dba)3 and 17 mg (0.03 mmol) of Xantphos and heat the reaction mixture for 6 h at 70° C. while stirring. Then distribute the mixture in 100 mL of ether/EtOAc 1:1 mixture and 50 mL of a saturated aqueous solution of NH4Cl. After extraction, wash the organic phase with 2×50 mL of water, dry over Na2SO4 and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a heptane/EtOAc gradient from 0 to 30% of EtOAc. After concentration under reduced pressure, we obtain 293 mg of methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-(2-oxopyrrolidin-1-yl)pyridine-2-carboxylate in the form of oil.

Workup

  1. customwhile bubbling with argon
  2. extractionAfter extraction
  3. washwash the organic phase with 2×50 mL of water
  4. dry with materialdry over Na2SO4
  5. concentrationconcentrate under reduced pressure
  6. customPurify the residue
  7. customobtained by silica gel column chromatography
  8. washeluting with a heptane/EtOAc gradient from 0 to 30% of EtOAc
  9. concentrationAfter concentration under reduced pressure, we

Sources & evidence

ORD record
ord-298f179eb9f541a2a6700e57e9148b3b
Source dataset
uspto-grants-2013_10
Patent number
US08552201B2

Reaction notes

Loading…