Thionyl Chloride → HCID 178440617, compound

HRID 1616685Notes

Reaction equation

HRID 1616685 reaction equation
O=S(Cl)Cl.[OH:5][C:6]1[C:11]2[CH2:12][C@@H:13]3[C:18]([CH3:20])([CH3:19])[C@:17]([CH3:21])([C:10]=2[CH:9]=[CH:8][CH:7]=1)[CH2:16][CH2:15][N:14]3[C:22]([C@@H:24]1[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26][CH2:25]1)=[O:23]>C(O)(C)(C)C>[C:10]([C:7]1[CH:8]=[CH:9][C:10]2[C@@:17]3([CH3:21])[C:18]([CH3:20])([CH3:19])[C@H:13]([N:14]([C:22]([C@@H:24]4[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26][CH2:25]4)=[O:23])[CH2:15][CH2:16]3)[CH2:12][C:11]=2[C:6]=1[OH:5])([CH3:17])([CH3:11])[CH3:9]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 178427878HCID 178427878, compound

Product 1

HCID 178440617HCID 178440617, compound

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
-10 °C

Procedure

SOCl2 (1 mL) is added dropwise to a solution of cis-4-[(2R,6S)-10-hydroxy-6,11,11-trimethyl-1,2,5,6-tetrahydro-4H-2,6-methano-benzo[d]azocine-3-carbonyl]-cyclohexane carboxylic acid (100 mg) in tert-butanol (5 mL) cooled to −10° C. Then, the cooling bath is removed and the resulting solution is stirred at ambient temperature overnight before another portion of SOCl2 (1 mL) is added. After stirring for additional 12 h more SOCl2 (2 mL) is added and the solution is heated to 50° C. The solution is stirred at this temperature for 48 h before HCl in 1,4-dioxane (1 mL) is added. The resulting solution is stirred at reflux temperature overnight and then treated with concentrated H2SO4 (3 mL). After stirring at reflux temperature for additional 3 h, the solution is cooled to ambient temperature and concentrated under reduced pressure. The residue is treated with water and the precipitate is separated by filtration. The precipitate is taken up in ethyl acetate and washed with water and dried (MgSO4). After removing the solvent, the residue is purified by HPLC (water/MeCN/F3CCO2H).

Workup

  1. customThen, the cooling bath is removed
  2. additionis added
  3. stirringAfter stirring for additional 12 h more SOCl2 (2 mL)
  4. additionis added
  5. temperaturethe solution is heated to 50° C
  6. stirringThe solution is stirred at this temperature for 48 h before HCl in 1,4-dioxane (1 mL)
  7. additionis added
  8. stirringThe resulting solution is stirred
  9. temperatureat reflux temperature overnight
  10. additiontreated with concentrated H2SO4 (3 mL)
  11. stirringAfter stirring
  12. temperatureat reflux temperature for additional 3 h
  13. temperaturethe solution is cooled to ambient temperature
  14. concentrationconcentrated under reduced pressure
  15. additionThe residue is treated with water
  16. customthe precipitate is separated by filtration
  17. washwashed with water
  18. dry with materialdried (MgSO4)
  19. customAfter removing the solvent
  20. customthe residue is purified by HPLC (water/MeCN/F3CCO2H)

Sources & evidence

ORD record
ord-087ec9cad268484282f5f161a1c8b71b
Source dataset
uspto-grants-2014_07
Patent number
US08765780B2

Reaction notes

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