Sulfuric Acid → HCID 90729371, compound

HRID 2193863Notes

Reaction equation

HRID 2193863 reaction equation
[CH3:1][C@H:2]([C:15]([OH:17])=[O:16])[C:3]1[CH:8]=[CH:7][C:6]2[CH:9]=[C:10](OC)[CH:11]=[CH:12][C:5]=2[CH:4]=1.C(O)CC[CH2:21][OH:22].S(=O)(=O)(O)[OH:25].[C:29]1(C)C=C[CH:32]=[CH:31][CH:30]=1>CCCCCC.O>[CH3:21][O:22][C:4]1[C:5]2[C:6](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:8][C:3]=1[C@H:2]([CH3:1])[C:15]([O:17][CH2:29][CH2:30][CH2:31][CH2:32][OH:25])=[O:16]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 1140TolueneHCID 80641,4-ButanediolHCID 156391Naproxen

Product 1

HCID 90729371HCID 90729371, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8058HexaneSolvent

Conditions

Temperature
80 °C

Procedure

Preparation based on patent WO 03/045896: 50 g of (S)—Naproxen are mixed with 196 g of 1,4-butanediol and the stirred mixture to is heated at 80° C. 0.42 g of sulfuric acid are added and the resulting mixture is stirred at 80° C. for 6.5 hours. After cooling at 50° C., toluene (33 g), water (35 g) and hexane (67 g) are added and the resulting two phase-system is stirred for 30 min. After phase separation, toluene (25 g) and hexane (25 g) are added to the aqueous layer at 50° C. The two phase system is stirred for 15 min. After phase separation, the aqueous layer is again extracted twice with toluene (25 g) and hexane (25 g). Toluene (130 g) and 0.2 M aqueous potassium carbonate (149 g) are added to the aqueous layer at 50° C. and the resulting two phase system is stirred for 30 min before phase separation. Water (150 g) is added to the organic layer and the resulting two phase system is stirred for 15 min before phase separation. This extraction is repeated again, with 150 g of water. The organic phase is evaporated under vacuum to get an oily residue. The HPLC purify of the product is 99%.

Workup

  1. customPreparation
  2. temperatureAfter cooling at 50° C.
  3. stirringthe resulting two phase-system is stirred for 30 min
  4. customAfter phase separation, toluene (25 g) and hexane (25 g)
  5. additionare added to the aqueous layer at 50° C
  6. stirringThe two phase system is stirred for 15 min
  7. customAfter phase separation
  8. extractionthe aqueous layer is again extracted twice with toluene (25 g) and hexane (25 g)
  9. additionToluene (130 g) and 0.2 M aqueous potassium carbonate (149 g) are added to the aqueous layer at 50° C.
  10. stirringthe resulting two phase system is stirred for 30 min before phase separation
  11. additionWater (150 g) is added to the organic layer
  12. stirringthe resulting two phase system is stirred for 15 min before phase separation
  13. extractionThis extraction
  14. customThe organic phase is evaporated under vacuum
  15. customto get an oily residue
  16. customThe HPLC purify of the product

Sources & evidence

ORD record
ord-7b06cbd0abaf474db1c495cfa7765815
Source dataset
uspto-grants-2012_12
Patent number
US08329937B2

Reaction notes

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