Dimethylformamide → tert-Butyl 1-(4-cyanophenyl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

HRID 535777Notes

Reaction equation

HRID 535777 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:22])[CH:9]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][CH:3]=1.[CH3:23][N:24](C=O)C>O.[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:23]([C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:22])[CH:9]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][CH:3]=1)#[N:24]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 684053282-(Boc-amino)-2-t-butyl-1-(4-chlorophenyl)ethanone

Product 1

HCID 68404944tert-Butyl 1-(4-cyanophenyl)-3,3-dimethyl-1-oxobutan-2-ylcarbamateYield 43%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

tert-Butyl 1-(4-chlorophenyl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (Example 2a, 2.30 g, 7.06 mmol) and Zn(CN)2 (0.87 g, 7.4 mmol) were dissolved in DMF (20 mL) under N2 (g). Pd(PPh3)4 (0.86 g, 0.74 mmol) was added and the mixture was heated at 130° C. overnight. The mixture was cooled to rt, diluted with water and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and evaporated. The product was purified on a silica column (EtOAc:hexane 1:10) to give tert-butyl 1-(4-cyanophenyl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (961 mg, 43%). tert-Butyl 1-(4-cyanophenyl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (961 mg, 3.04 mmol) was dissolved in 1.25 M HCl in MeOH at 0° C. and the mixture was stirred at rt for 8 h. The solvent was removed and the residue dried in vacuo to give 4-(2-amino-3,3-dimethyl-butanoyl)-benzonitrile hydrochloride (110 mg, 93%).

Workup

  1. temperatureThe mixture was cooled to rt
  2. extractionextracted with EtOAc
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe product was purified on a silica column (EtOAc:hexane 1:10)

Sources & evidence

ORD record
ord-ec91184890b740d5a6e6411a50334ebe
Source dataset
uspto-grants-2014_10
Patent number
US08859556B2

Reaction notes

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