Dimethylformamide → tert-Butyl [1-(4-cyanophenyl)cyclobutyl]carbamate

HRID 2362147Notes

Reaction equation

HRID 2362147 reaction equation
[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15](Cl)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:20][N:21](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[Zn].O>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:20]#[N:21])=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 2

HCID 6228DimethylformamideHCID 57805484tert-Butyl [1-(4-chlorophenyl)cyclobutyl]carbamate

Product 1

HCID 46856381tert-Butyl [1-(4-cyanophenyl)cyclobutyl]carbamate

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Procedure

A mixture of [1-(4-Chloro-phenyl)-cyclobutyl]-carbamic acid tert-butyl ester 1-1 (prepared according to WO2008/070016; 1.57 g, 5.6 mmol), Zn(CN)2 (395 mg, 3.37 mmol), Pd2(dba)3 (257 mg, 0.28 mmol), dppf (311 mg, 0.56 mmol), Zinc powder (219 mg, 3.37 mmol) and 20 mL of DMF was heated to 100.deg.C for 2 hrs under nitrogen atmosphere. After cooling to room temperature, the mixture was poured into water and extracted with EA for three times. The combined EA layer was washed with water, brine and concentrated to give a residue, which was purified by silica gel chromatography eluting with EA/PE (3/1) to give 1.23 g of compound 1-2. MS (ESI) m/e (M+H+): observed=273.2, calculated=273.2.

Workup

  1. temperaturewas heated to 100.deg.C for 2 hrs under nitrogen atmosphere
  2. extractionextracted with EA for three times
  3. washThe combined EA layer was washed with water, brine
  4. concentrationconcentrated
  5. customto give a residue, which
  6. customwas purified by silica gel chromatography
  7. washeluting with EA/PE (3/1)

Sources & evidence

ORD record
ord-310dc2dc7840431fac8f42913c8642d9
Source dataset
uspto-grants-2014_04
Patent number
US08691825B2

Reaction notes

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