Dimethylformamide → Biphenyl-2-ylcarbamic acid 1-[2-(4-iodo-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester

HRID 1094967Notes

Reaction equation

HRID 1094967 reaction equation
[I:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C:10](=[O:13])[CH:11]=[CH2:12])=[C:4]([CH3:14])[CH:3]=1.CN(C)C=O.[NH:20]1[CH2:25][CH2:24][CH:23]([O:26][C:27](=[O:41])[NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:22][CH2:21]1>C(O)(C)C>[I:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C:10]([CH2:11][CH2:12][N:20]2[CH2:21][CH2:22][CH:23]([O:26][C:27](=[O:41])[NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH2:24][CH2:25]2)=[O:13])=[C:4]([CH3:14])[CH:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 10851461Biphenyl-2-ylcarbamic Acid Piperidin-4-yl EsterHCID 57461079N-(4-iodo-2,5-dimethylphenyl)acrylamide

Product 1

HCID 46239622Biphenyl-2-ylcarbamic acid 1-[2-(4-iodo-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl esterYield 93.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of N-(4-iodo-2,5-dimethylphenyl)acrylamide (32.2 g, 107 mmol) in a 6:1 v/v mixture of N,N-dimethylformamide and isopropanol (700 mL) was added biphenyl-2-ylcarbamic acid piperidin-4-yl ester (36.3 g, 123 mmol). The resulting mixture was heated at 50° C. for 24 hours and then at 80° C. for 24 hours. The reaction mixture was then cooled to room temperature and concentrated under vacuum. The residue was dissolved in dichloromethane (1 L) and this solution was washed with 1N aqueous hydrochloric acid (500 mL), water (500 mL), brine (500 mL) and saturated aqueous sodium bicarbonate solution (500 mL). The organic layer was then dried over anhydrous magnesium sulfate and filtered. Ethanol (400 mL) was added and the resulting mixture was concentrated under vacuum to a volume of about 400 mL, at which time a precipitate had formed. The precipitate was filtered and dried to afford biphenyl-2-ylcarbamic acid 1-[2-(4-iodo-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester (59.6 g, 84% purity, 79% yield). m/z: [M+H+] calcd for C29H32IN3O3 598.49; found 598.5.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. concentrationconcentrated under vacuum
  3. dissolutionThe residue was dissolved in dichloromethane (1 L)
  4. washthis solution was washed with 1N aqueous hydrochloric acid (500 mL), water (500 mL), brine (500 mL) and saturated aqueous sodium bicarbonate solution (500 mL)
  5. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. additionEthanol (400 mL) was added
  8. concentrationthe resulting mixture was concentrated under vacuum to a volume of about 400 mL, at which time a precipitate
  9. customhad formed
  10. filtrationThe precipitate was filtered
  11. customdried

Sources & evidence

ORD record
ord-a9715669ac2642e6a87b532c1721f35e
Source dataset
uspto-grants-2012_03
Patent number
US08134006B2

Reaction notes

Loading…