Hydrochloric Acid → HCID 178464415, compound

HRID 1192515Notes

Reaction equation

HRID 1192515 reaction equation
[NH2:1][C:2]1[C:3]([C:20]#[C:21][Si:22]([CH3:25])([CH3:24])[CH3:23])=[C:4]([Cl:19])[CH:5]=[C:6]([C:15]([O:17][CH3:18])=[O:16])[C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=1.Cl.[N:27]([O-])=O.[Na+].[CH2:31]([NH:33][CH2:34][CH3:35])[CH3:32].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(#N)C.O.C(=O)(O)[O-].[Na+]>[Cl:19][C:4]1[CH:5]=[C:6]([C:15]([O:17][CH3:18])=[O:16])[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[C:2](/[N:1]=[N:27]/[N:33]([CH2:34][CH3:35])[CH2:31][CH3:32])[C:3]=1[C:20]#[C:21][Si:22]([CH3:23])([CH3:25])[CH3:24]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 8021DiethylamineHCID 11430Potassium CarbonateHCID 23668193Sodium NitriteHCID 58368604HCID 58368604, compound

Product 1

HCID 178464415HCID 178464415, compoundYield 86%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent4×HCID 6342AcetonitrileSolvent3×HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-5 °C

Procedure

A solution of methyl 6-amino-4-chloro-3′-fluoro-5-[(trimethylsilyl)ethynyl]biphenyl-2-carboxylate (3.2 g, 8.4 mmol) in tetrahydrofuran (8.1 mL), acetonitrile (8.1 mL), and water (9.3 mL) was cooled to −5° C. and treated with 12 M of hydrogen chloride in water (5.6 mL, 68 mmol) dropwise followed by a solution of sodium nitrite (1.2 g, 17 mmol) in water (6.3 mL)/acetonitrile (2.1 mL) and stirred at −5° C. for 30 minutes. This mixture was added to a solution of diethylamine (8.7 mL, 84 mmol) and potassium carbonate (7.0 g, 51 mmol) in water (76 mL)/acetonitrile (25 mL) that was cooled at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes and warmed to 20° C. The reaction mixture was diluted with saturated sodium bicarbonate (100 mL) and extracted with ethyl acetate (200 mL). The organic layer was separated, washed with brine, dried with sodium sulfate, filtered, and concentrated to a crude oil. Purification by flash column chromatography using dichloromethane in hexanes (0%-50%) gave the desired product (3.3 g, 86%). LCMS for C23H28ClFN3O2Si (M+H)+: m/z=460.2; Found: 459.8.

Workup

  1. temperaturewas cooled at 0° C
  2. stirringThe reaction mixture was stirred at 0° C. for 30 minutes
  3. temperaturewarmed to 20° C
  4. extractionextracted with ethyl acetate (200 mL)
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a crude oil
  10. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-aa07c26087e649dc95d5823506e0809c
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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