Ethanol → [4-(3'-Cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-carbamic acid isobutyl ester

HRID 2180179Notes

Reaction equation

HRID 2180179 reaction equation
[CH2:1]([O:5][C:6](=[O:26])[NH:7][CH2:8][C:9]1([C:19]2[CH:24]=[CH:23][C:22](I)=[CH:21][CH:20]=2)[CH2:14][CH2:13][N:12]([CH2:15][CH:16]2[CH2:18][CH2:17]2)[CH2:11][CH2:10]1)[CH:2]([CH3:4])[CH3:3].[C:27]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)#[N:28].C([O-])([O-])=O.[Na+].[Na+].CCO>C1(C)C=CC=CC=1.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.O>[CH2:1]([O:5][C:6](=[O:26])[NH:7][CH2:8][C:9]1([C:19]2[CH:24]=[CH:23][C:22]([C:33]3[CH:32]=[CH:31][CH:30]=[C:29]([C:27]#[N:28])[CH:34]=3)=[CH:21][CH:20]=2)[CH2:14][CH2:13][N:12]([CH2:15][CH:16]2[CH2:18][CH2:17]2)[CH2:11][CH2:10]1)[CH:2]([CH3:4])[CH3:3]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 68533264[1-Cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-carbamic acid isobutyl ester

Product 1

HCID 20779461[4-(3'-Cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-carbamic acid isobutyl esterYield 24.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a flask containing [1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-carbamic acid isobutyl ester (0.061 g, 0.13 mmol) was added Pd(PPh3)4 (0.015 g, 0.013 mmol, 10 mol %), 3-cyanophenylboronic acid (0.03 g, 0.2 mmol, 1.5 eq.) and Na2CO3 (0.212 g, 2 mmol). The mixture was suspended in toluene (3 mL), EtOH (1.5 mL) and H2O (1.0 mL) and heated to 80° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (10 mL) and saturated Na2CO3 (10 mL). The organic layer was washed with saturated Na2CO3 (3×10 mL) and saturated brine (2×10 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product. This was purified by HPLC to give the title compound [4-(3′-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-carbamic acid isobutyl ester as a brown solid (0.014 g, 24%). MS (ESI): 446.3/447.3 (M+1).

Workup

  1. custompartitioned between EtOAc (10 mL) and saturated Na2CO3 (10 mL)
  2. washThe organic layer was washed with saturated Na2CO3 (3×10 mL) and saturated brine (2×10 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customThis was purified by HPLC

Sources & evidence

ORD record
ord-f943e85fb1d74fb498d78f5cdbe15da0
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

Loading…