Triethylamine → Cis-N-(6-benzhydryl-tetrahydropyran-3-yl)-2-(4-fluoro-phenyl)-acetamide

HRID 78912Notes

Reaction equation

HRID 78912 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH:18]([C@H:31]1[O:36][CH2:35][C@@H:34]([NH2:37])[CH2:33][CH2:32]1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(CC)CC)C>ClCCl.CN(C=O)C>[CH:18]([C@H:31]1[O:36][CH2:35][C@@H:34]([NH:37][C:9](=[O:11])[CH2:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:33][CH2:32]1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 98372-(4-Fluorophenyl)acetic acidHCID 65578Oxalyl chlorideHCID 11565229Cis-(6-benzhydryl-tetrahydropyran-3-yl)-amine

Product 1

HCID 66631371Cis-N-(6-benzhydryl-tetrahydropyran-3-yl)-2-(4-fluoro-phenyl)-acetamideYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent4×

Procedure

Into a solution of 4-fluorophenylacetic acid (0.23 g, 1.46 mmol) in dichloromethane (25 ml) was added oxalyl chloride (0.22 g, 1.76 mmol) dissolved in dichloromethane (5 ml) at 0° C. which was followed by addition of one drop of DMF. The reaction mixture was allowed to reach at room temperature over a period of 2 hours. The solvent was removed in vacuo, and the residue was dissolved in dichloromethane (5 ml) and was added into a solution of cis-N-(6-benzhydryl-tetrahydropyran-3-yl)-amine (0.26 g, 0.96 mmol) and triethylamine (0.31 g, 1.46 mmol) in dichloromethane (25 ml) at 0° C. After 20 minutes the reaction mixture was allowed to come to room temperature. After 3 hours, more dichloromethane was added and the mixture was washed in turn with 1N NaHCO3, H2O and brine, then dried over anhydrous Na2SO4. The solvent was removed in vacuo, and the residue was purified by flash chromatography (hexane/ethyl acetate 7:3) to give cis-N-(6-benzhydryl-tetrahydropyran-3-yl)-2-(4-fluorophenyl)-acetamide 17 (0.31 g, yield 80%) as an oil.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in dichloromethane (5 ml)
  3. waitAfter 20 minutes the reaction mixture was allowed
  4. customto come to room temperature
  5. waitAfter 3 hours
  6. washthe mixture was washed in turn with 1N NaHCO3, H2O and brine
  7. dry with materialdried over anhydrous Na2SO4
  8. customThe solvent was removed in vacuo
  9. customthe residue was purified by flash chromatography (hexane/ethyl acetate 7:3)

Sources & evidence

ORD record
ord-486e471d1cd84872bf1bced4c0c364f4
Source dataset
uspto-grants-2014_09
Patent number
US08841464B2

Reaction notes

Loading…