Hydrochloric Acid → HCID 58002981, compound

HRID 1516689Notes

Reaction equation

HRID 1516689 reaction equation
[CH:1]1([C:6]2[CH:15]=[C:14]3[C:9]([C@@H:10]([OH:18])[CH2:11][C:12]([CH3:17])([CH3:16])[O:13]3)=[C:8]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:7]=2[C:26]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[O:27])[CH2:5][CH2:4][CH2:3][CH2:2]1.CC1C=CC=C(C)N=1.FC(F)(F)S(O[Si:52]([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53])(=O)=O.Cl>C1(C)C=CC=CC=1>[Si:52]([O:18][C@@H:10]1[C:9]2[C:14](=[CH:15][C:6]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[C:7]([C:26]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:30][CH:29]=3)=[O:27])[C:8]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[O:13][C:12]([CH3:16])([CH3:17])[CH2:11]1)([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonate2×HCID 25022900[(4S)-7-Cyclopentyl-5-(4-fluorophenyl)-4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl][4-(trifluoromethyl)phenyl]methanone

Product 1

HCID 58002981HCID 58002981, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-20 °C

Procedure

Under argon, 200 mg (0.39 mmol) of [(4S)-7-cyclopentyl-5-(4-fluorophenyl)-4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl][4-(trifluoromethyl)phenyl]methanone (Example 12A) and 180 μl (1.56 mmol) of 2,6-dimethylpyridine are dissolved in 1.25 ml of toluene and cooled to −20° C. A solution of 0.18 ml (0.78 mmol) of tert-butyldimethylsilyl trifluoromethanesulfonate in 1.25 ml of toluene is added dropwise, and the mixture is stirred at −20° C. for 15 min, then warmed to 0° C. and stirred for 1 hour. Another 18 μl (0.078 mmol) of tert-butyldimethylsilyl trifluoromethanesulfonate are added, and stirring is continued for another 1.5 h. 5 ml of 0.1 N hydrochloric acid are added, and the mixture is extracted repeatedly with ethyl acetate. The organic phases are washed with a 1:1 mixture of saturated sodium bicarbonate solution and saturated sodium chloride solution and with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 15:1). This gives 227 mg (93% of theory) of the title compound.

Workup

  1. temperaturewarmed to 0° C.
  2. stirringstirred for 1 hour
  3. stirringstirring
  4. waitis continued for another 1.5 h
  5. extractionthe mixture is extracted repeatedly with ethyl acetate
  6. washThe organic phases are washed with a 1:1 mixture of saturated sodium bicarbonate solution and saturated sodium chloride solution and with saturated sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 15:1)

Sources & evidence

ORD record
ord-e7c55ef13d444cd9a4a6121bee3e7c10
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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