Potassium Carbonate → (S)-tert-Butyl 1-cyano-2-(4'-cyano-3'-fluorobiphenyl-4-yl)ethylcarbamate

HRID 600296Notes

Reaction equation

HRID 600296 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][C:4]=1[F:12])#[N:2].[C:13]([C@@H:15]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:16][C:17]1[CH:22]=[CH:21][C:20](I)=[CH:19][CH:18]=1)#[N:14].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[C:13]([C@@H:15]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([F:12])[CH:5]=2)=[CH:19][CH:18]=1)#[N:14]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 57999650(S)-Tert-butyl (1-cyano-2-(4-iodophenyl)ethyl)carbamate

Product 1

HCID 57999694(S)-tert-Butyl 1-cyano-2-(4'-cyano-3'-fluorobiphenyl-4-yl)ethylcarbamateYield 38.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 4-cyano-3-fluorophenylboronic acid (0.736 g) dissolved in dioxane (10 mL) was added to a stirred solution of (S)-tert-butyl 1-cyano-2-(4-iodophenyl)ethylcarbamate (1.51 g) and bis[bis(1,2-diphenylphosphino)ethane]palladium (0) (0.037 g) in dioxane (20 mL) under nitrogen. The resulting mixture was stirred for 10 min. A solution of potassium carbonate (1.121 g) in water (5 mL) was added and the resulting solution was stirred at 75° C. for 3 h. The cooled mixture was evaporated to dryness. The residue was taken up in ethyl acetate (150 mL) and washed with saturated brine (3×50 mL), dried over sodium sulfate and adsorbed onto silica. The crude product was purified by flash silica chromatography, eluting with 20% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford the subtitle compound as a colourless solid (0.568 g).

Workup

  1. stirringthe resulting solution was stirred at 75° C. for 3 h
  2. customThe cooled mixture was evaporated to dryness
  3. washwashed with saturated brine (3×50 mL)
  4. dry with materialdried over sodium sulfate
  5. customThe crude product was purified by flash silica chromatography
  6. washeluting with 20% ethyl acetate in isohexane
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-107c8110e54a4d12bf20c3dd5054478c
Source dataset
uspto-grants-2011_03
Patent number
US07902181B2

Reaction notes

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