Trifluoroacetic acid → HCID 131736057, compound

HRID 1050265Notes

Reaction equation

HRID 1050265 reaction equation
[C:1]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:6]=[CH:5][C:4]([C:7]2[N:12]=[C:11]3[N:13]=[C:14]([O:24][C@H:25]4[CH2:34][O:33][C@H:32]5[C@@H:27]([O:28]C(C6C=CC=CC=6)[O:30][CH2:31]5)[CH2:26]4)[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:10]3=[CH:9][C:8]=2[Cl:41])=[CH:3][CH:2]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[C:1]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:6]=[CH:5][C:4]([C:7]2[N:12]=[C:11]3[N:13]=[C:14]([O:24][C@H:25]4[CH2:34][O:33][C@H:32]([CH2:31][OH:30])[C@@H:27]([OH:28])[CH2:26]4)[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:21])[CH3:22])[C:10]3=[CH:9][C:8]=2[Cl:41])=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12052TriethylsilaneHCID 89558174HCID 89558174, compound

Product 1

HCID 131736057HCID 131736057, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 5-([1,1′-biphenyl]-4-yl)-6-chloro-2-(((4aR,7R,8aS)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)oxy)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine (476 mg, 0.710 mmol) under nitrogen in anhydrous DCM (6.0 mL) was added 4A molecular sieves (1.6 g). The mixture was cooled to 0° C., then triethylsilane (0.85 mL, 619 mg, 5.33 mmol) and TFA (0.41 mL, 607 mg, 5.33 mmol) were added. The mixture was stirred at 0° C. for 1.5 hours, and then allowed to stir 1 hour at room temperature. The mixture was then cooled to 0° C. and a saturated aqueous solution of potassium carbonate (30 mL) was added dropwise over 3 minutes. After stirring at room temperature for an additional 5 minutes, the mixture was filtered, diluted with saturated aqueous sodium bicarbonate (30 mL), and extracted with ethyl acetate (2×150 mL). The combined organic layers were washed with brine (60 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resultant residue was chromatographed using a Biotage™ 25 g silica gel cartridge eluted with 0-100% EtOAc in 1:1 Hexane/DCM over 25 column volumes with a 15 column volume hold at 100% EtOAc. The product fractions were combined and concentrated under reduced pressure to give the desired product as a white solid. LC-MS: calculated for C30H36ClN3O5Si 581.21, observed m/e: 582.31 (M+H)+ (Rt 2.66/4 min).

Workup

  1. stirringto stir 1 hour at room temperature
  2. temperatureThe mixture was then cooled to 0° C.
  3. stirringAfter stirring at room temperature for an additional 5 minutes
  4. filtrationthe mixture was filtered
  5. additiondiluted with saturated aqueous sodium bicarbonate (30 mL)
  6. extractionextracted with ethyl acetate (2×150 mL)
  7. washThe combined organic layers were washed with brine (60 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resultant residue was chromatographed
  11. washeluted with 0-100% EtOAc in 1:1 Hexane/DCM over 25 column volumes with a 15 column volume hold at 100% EtOAc
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c62d111cc6274aa5a2738fe954258226
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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