Ammonium Chloride → HCID 71765803, compound

HRID 338317Notes

Reaction equation

HRID 338317 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-b1bed71bc7ea4f03baf68fcd7fd9d78c
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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