Potassium Carbonate → HCID 67257612, compound

HRID 1476662Notes

Reaction equation

HRID 1476662 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](=[O:32])(=[O:31])[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>[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](=[O:32])(=[O:31])[CH2:13][C@@H:12]3[C:6]=2[CH:5]=1)[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 24813Phosphorus oxychlorideHCID 67257636HCID 67257636, compound2×

Product 1

HCID 67257612HCID 67257612, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred mixture of methyl 4-{[(3R,4R)-3-(3-ethoxy-4-methoxyphenyl)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]carbamoyl}benzoate (22.8 g; compound C4) and K2CO3 (6.82 g) in absolute ACN (200 ml) is added POCl3 (13.6 ml) at 0° C. (ice bath). The suspension is allowed to come to RT within 1 h and is subsequently refluxed at 85° C. for 6 h. Afterwards the mixture is stirred for 12 h at RT under nitrogen atmosphere. The mixture is quenched with water (500 ml) and adjusted to pH7 by addition of 0.4 M NaOH. The ACN is destilled of and to the remaining suspension DCM (500 ml) is added. The pH value is adjusted to 8.1 by addition of aqueous sodium hydroxide solution (0.4 M) and saturated aqueous solution of sodium bicarbonate and the mixture is stirred at RT for 12 h. The organic layer is separated and the aqueous layer is extracted with DCM (300 ml). The combined organic layers are dried over sodium sulfate, filtered and evaporated in vacuo to dryness. The resulting residue is purified by flash column chromatography [silica gel, eluent system: n-hexane/EtOAc/triethylamine 11/8/1 (v/v/v)] to obtain a crude solid. The residue is treated with DIP (400 ml) and stirred at reflux temperature for 3 h. The suspension is cooled to 0° C. with an ice bath and filtered off. The filter cake is washed with DIP and dried in vacuo at 70° C. to obtain the title compound as a solid.

Workup

  1. customThe mixture is quenched with water (500 ml)
  2. additionadjusted to pH7 by addition of 0.4 M NaOH
  3. additionis added
  4. additionThe pH value is adjusted to 8.1 by addition of aqueous sodium hydroxide solution (0.4 M) and saturated aqueous solution of sodium bicarbonate
  5. stirringthe mixture is stirred at RT for 12 h
  6. customThe organic layer is separated
  7. extractionthe aqueous layer is extracted with DCM (300 ml)
  8. dry with materialThe combined organic layers are dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo to dryness
  11. customThe resulting residue is purified by flash column chromatography [silica gel, eluent system: n-hexane/EtOAc/triethylamine 11/8/1 (v/v/v)]
  12. customto obtain a crude solid
  13. additionThe residue is treated with DIP (400 ml)
  14. stirringstirred
  15. temperatureat reflux temperature for 3 h
  16. temperatureThe suspension is cooled to 0° C. with an ice bath
  17. filtrationfiltered off
  18. washThe filter cake is washed with DIP
  19. customdried in vacuo at 70° C.

Sources & evidence

ORD record
ord-c1744a633f3f45249803d332cc12cb56
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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