Dimethylformamide → HCID 68185395, compound

HRID 2366859Notes

Reaction equation

HRID 2366859 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3].[CH3:23][N:24](C)C=O>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-]#N.[Zn+2].[C-]#N>[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:23]#[N:24])[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 68185395HCID 68185395, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

A solution of 1-methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Example 4) (355 mg, 0.962 mmol) in N,N-dimethylformamide (DMF) (5 mL) at room temperature was degassed over 30 min under house vacuum and quenched several times with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (116 mg, 0.1 mmol) and zinc(II) cyanide (153 mg, 1.3 mmol) were then added and the resulting yellow mixture was stirred under nitrogen at 100° C. for 5 h then cooled to room temperature. The insoluble were filtered off, rinsed with AcOEt then destroyed with bleach. The organic phase was washed with water. The aqueous phase was extracted with AcOEt. The combined organic phases were washed twice with water then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 10 G silica cartridge (gradient: 13 to 63% AcOEt in Hexanes) gave 1-methylethyl[(2S,4R)-1-acetyl-6-cyano-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (238 mg, 0.755 mmol, 78% yield) as a white solid.

Workup

  1. customat room temperature
  2. customwas degassed over 30 min under house vacuum
  3. customquenched several times with nitrogen
  4. temperaturethen cooled to room temperature
  5. filtrationThe insoluble were filtered off
  6. washrinsed with AcOEt
  7. customthen destroyed with bleach
  8. washThe organic phase was washed with water
  9. extractionThe aqueous phase was extracted with AcOEt
  10. washThe combined organic phases were washed twice with water
  11. dry with materialbrine, dried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customPurification of the residue by SP4

Sources & evidence

ORD record
ord-4c232665e32640f582853400198d4061
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…