Trimethyl orthoacetate → HCID 57965495, compound

HRID 1695552Notes

Reaction equation

HRID 1695552 reaction equation
CC1C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1.C[O:19][C:20](OC)(OC)[CH3:21].[F:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[C:41]3[CH:40]=[C:39]4[CH2:42][CH2:43][C@@H:44]5[C@@H:49]([C@@:38]4([CH3:60])[CH2:37][C:36]=3[CH:35]=[N:34]2)[C@@H:48]([OH:50])[CH2:47][C@:46]2([CH3:59])[C@:51]([C:55](=[O:58])[CH2:56][OH:57])([OH:54])[CH2:52][CH2:53][C@@H:45]52)=[CH:29][CH:28]=1.O.CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.O.CCOC(C)=O>[C:20]([O:54][C@@:51]1([C:55](=[O:58])[CH2:56][OH:57])[C@:46]2([CH3:59])[C@H:45]([C@H:44]3[C@H:49]([C@@H:48]([OH:50])[CH2:47]2)[C@@:38]2([CH3:60])[CH2:37][C:36]4[CH:35]=[N:34][N:33]([C:30]5[CH:29]=[CH:28][C:27]([F:26])=[CH:32][CH:31]=5)[C:41]=4[CH:40]=[C:39]2[CH2:42][CH2:43]3)[CH2:53][CH2:52]1)(=[O:19])[CH3:21]

Participants

9

Reactant 5

HCID 15050Trimethyl orthoacetateHCID 161440Pyridine 4-methylbenzene-1-sulfonateHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 11733546(11β)-2′-(4-Fluorophenyl)-11,17-21-trihydroxy-2′H-pregna-2,4-dieno[3,2-c]pyrazol-20-one

Product 1

HCID 57965495HCID 57965495, compoundYield 16.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

According to the literature (Chem. Pharm. Bull. 2006, 54(11), 1567-1570) pyridine 4-methylbenzenesulfonate (0.034 g, 0.14 mmol) and 1,1,1-trimethoxyethane (0.136 ml, 1.06 mmol) were added to a solution of 1-[(1R,3aS,3bS,10aR,10bS,11S,12aS)-7-(4-fluorophenyl)-1,11-dihydroxy-10a,12a-dimethyl-1,2,3,3a,3b,4,5,7,10,10a,10b,11,12,12a-tetradecahydrocyclopenta[5,6]naphtho[1,2-f]indazol-1-yl]-2-hydroxyethanone (Steroids 2003 (68) 177-191) (0.34 g, 0.71 mmol) in DCM (15 ml). The mixture was stirred at room temperature for 4 hours, concentrated under reduced pressure, the obtained residue was dissolved in acetone (10 ml) and 4-methyl benzenesulfonic acid hydrate (0.21 g, 1.10 mmol) dissolved in water (10 ml) was added while cooling in an ice-bath. The mixture was stirred for 60 min. at the same temperature followed by the addition of sat. NaHCO3 solution (15 ml) and subsequent extraction with EtOAc (30 ml). The organic layer was washed with brine, dried and purified on a preparative HPLC column (CH3CN/water) and the product containing fractions were freeze-dried to give 60 mg of the title compound.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionthe obtained residue was dissolved in acetone (10 ml)
  3. additionwas added
  4. temperaturewhile cooling in an ice-bath
  5. stirringThe mixture was stirred for 60 min. at the same temperature
  6. washThe organic layer was washed with brine
  7. customdried
  8. custompurified on a preparative HPLC column (CH3CN/water)
  9. additionthe product containing fractions
  10. customwere freeze-dried

Sources & evidence

ORD record
ord-3be0987c9d9b4b048cd7e31a68fe65ae
Source dataset
uspto-grants-2012_04
Patent number
US08163724B2

Reaction notes

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