Potassium Carbonate → HCID 70976078, compound

HRID 1476666Notes

Reaction equation

HRID 1476666 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@@H:12]2[C@H:17]([NH:18][C:19]([C:21]3[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][CH:22]=3)=O)[CH2:16][CH2:15][S:14][CH2:13]2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].C(=O)([O-])[O-].[K+].[K+].O=P(Cl)(Cl)Cl>C(#N)C.O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>[CH2:1]([O:3][C:4]1[C:9]([O:10][CH3:11])=[CH:8][C:7]2[C:19]([C:21]3[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][CH:22]=3)=[N:18][C@@H:17]3[CH2:16][CH2:15][S:14][CH2:13][C@@H:12]3[C:6]=2[CH:5]=1)[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 24813Phosphorus oxychlorideHCID 67257206HCID 67257206, compound

Product 1

HCID 70976078HCID 70976078, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 180504Ceric ammonium nitrateSolvent

Procedure

To a suspension of methyl 4-{[(3R,4R)-3-(3-ethoxy-4-methoxyphenyl)tetrahydro-2H-thiopyran-4-yl]carbamoyl}benzoate (20.5 g; compound C12) and potassium carbonate (6.6 g) in ACN (400 ml) is slowly added a solution of POCl3 (13.2 ml) in CAN (50 ml) at 0° C. Subsequently the mixture is heated under reflux for 17 h. The reaction is quenched by addition of water (300 ml) at RT and the pH value is adjusted to pH 7.6 by addition of a 40% aqueous sodium hydroxide solution. The acetonitrile is removed in vacuo and diethyl ether is added to the suspension. The pH is adjusted to pH 8.6 by further addition of a 40% aqueous sodium hydroxide solution and a saturated solution of sodium hydrogen carbonate. After extraction the organic phase is separated, washed with water and dried over sodium sulfate. Filtration and evaporation of the solvent give a solid that is purified by flash chromatography (silica gel, eluation gradient: n-hexane/isopropyl acetate, 19/1 to 12/8 (v/v)) to yield the title compound as a solid.

Workup

  1. temperatureSubsequently the mixture is heated
  2. temperatureunder reflux for 17 h
  3. customThe reaction is quenched by addition of water (300 ml) at RT
  4. additionthe pH value is adjusted to pH 7.6 by addition of a 40% aqueous sodium hydroxide solution
  5. customThe acetonitrile is removed in vacuo and diethyl ether
  6. additionis added to the suspension
  7. additionThe pH is adjusted to pH 8.6 by further addition of a 40% aqueous sodium hydroxide solution
  8. extractionAfter extraction the organic phase
  9. customis separated
  10. washwashed with water
  11. dry with materialdried over sodium sulfate
  12. filtrationFiltration and evaporation of the solvent
  13. customgive a solid
  14. customthat is purified by flash chromatography (silica gel, eluation gradient: n-hexane/isopropyl acetate, 19/1 to 12/8 (v/v))

Sources & evidence

ORD record
ord-86bc8e6a97724e62b73553f509062c9b
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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