Ammonium Chloride → HCID 71765803, compound

HRID 1054660Notes

Reaction equation

HRID 1054660 reaction equation
[Si]([O:8][CH2:9][C:10]([C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][C:27]=2[Cl:28])[NH:24][CH:23]=[C:22]3[C:29]([OH:31])=[O:30])=[CH:15][CH:14]=1)([CH3:12])[CH3:11])(C(C)(C)C)(C)C.[F-].[Cs+].[Cl-].[NH4+]>CN(C=O)C>[Cl:28][C:27]1[CH:26]=[C:25]2[C:21]([C:22]([C:29]([OH:31])=[O:30])=[CH:23][NH:24]2)=[CH:20][C:19]=1[C:16]1[CH:17]=[CH:18][C:13]([C:10]([CH3:12])([CH3:11])[CH2:9][OH:8])=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 25953Cesium fluorideHCID 86698663HCID 86698663, compound

Product 1

HCID 71765803HCID 71765803, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-[4-(1-{[tert-butyl(dimethyl)silyl]oxy}-2-methylpropan-2-yl)phenyl]-6-chloro-1H-indole-3-carboxylic acid (76 mg, 0.17 mmol) in DMF (0.55 mL) was treated with solid cesium fluoride (507 mg, 3.32 mmol) and stirred at room temperature for one hour. The reaction mixture was then heated at 60° C. for two hours, then at 50° C. for two hours. The cooled reaction mixture was then poured into saturated ammonium chloride solution (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated to give the title compound as an orange oil. The crude product was dissolved in DMSO (1.8 mL) and 0.9 mL of this solution was purified using reverse-phase chromatography to give the title Compound. MS (ES−) 342.0 (M−H)−. Retention time: 1.61 min; Waters Xbridge dC18 5 μm 4.6×50 mm, 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. (0.03% NH4OH). Flow: 2.0 mL/min.

Workup

  1. temperatureThe reaction mixture was then heated at 60° C. for two hours
  2. waitat 50° C. for two hours
  3. customThe cooled reaction mixture
  4. extractionextracted with ethyl acetate (3×20 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-537a877a180347399f6ec46bf48cfb22
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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