Dimethylformamide → tert-Butyl (6-cyano-1,2,3,4-tetrahydroquinolin-3-yl)carbamate

HRID 2234244Notes

Reaction equation

HRID 2234244 reaction equation
[C:1]([O:5][C:6](=[O:19])[NH:7][CH:8]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:20][N:21](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6](=[O:19])[NH:7][CH:8]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:20]#[N:21])[CH:15]=2)[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 17758659tert-Butyl (6-bromo-1,2,3,4-tetrahydroquinolin-3-yl)carbamate

Product 1

HCID 66692977tert-Butyl (6-cyano-1,2,3,4-tetrahydroquinolin-3-yl)carbamateYield 67%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

A solution of (6-bromo-1,2,3,4-tetrahydroquinolin-3-yl)-carbamic acid tert-butyl ester (250 mg, 0.76 mmol), prepared as described in Example 1B, and zinc cyanide (88 mg, 0.75 mmol) in DMF (2.5 mL) was bubbled with argon for 10 min, then tetrakis-(triphenylphosphine) palladium(0) (65 mg, 0.057 mmol) was added and the solution was deoxygenated. The reaction mixture was then heated at 90° C. for 4 h, cooled to RT, and partitioned between EtOAc and water. The aqueous layer was separated and extracted with EtOAc (2×20 mL). The combined EtOAc extracts were washed with saturated aqueous NaCl, dried Na2SO4) and concentrated. The residue was chromatographed (silica gel) eluting with EtOAc (0 to 60%) in hexanes to give the title compound (140 mg, 67% yield) as a white solid.

Workup

  1. customwas bubbled with argon for 10 min
  2. customthe solution was deoxygenated
  3. temperaturecooled to RT
  4. custompartitioned between EtOAc and water
  5. customThe aqueous layer was separated
  6. extractionextracted with EtOAc (2×20 mL)
  7. washThe combined EtOAc extracts were washed with saturated aqueous NaCl, dried Na2SO4) and
  8. concentrationconcentrated
  9. customThe residue was chromatographed (silica gel)
  10. washeluting with EtOAc (0 to 60%) in hexanes

Sources & evidence

ORD record
ord-b8093090d8ed45db91c0c980f577d35b
Source dataset
uspto-grants-2010_05
Patent number
US07709647B2

Reaction notes

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