Cesium carbonate → 2-(1-Bromo-6-{[(4-cyclohexyl-benzoyl)-methyl-amino]-methyl}-naphthalen-2-yloxy)-3-phenyl-propionic acid methyl ester

HRID 1357306Notes

Reaction equation

HRID 1357306 reaction equation
[Br:1][C:2]1[C:11]([OH:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH2:13][N:14]([CH3:29])[C:15](=[O:28])[C:16]1[CH:21]=[CH:20][C:19]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=1)=[CH:7]2.[CH3:30][O:31][C:32](=[O:49])[CH:33](OS(C(F)(F)F)(=O)=O)[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[CH3:30][O:31][C:32](=[O:49])[CH:33]([O:12][C:11]1[CH:10]=[CH:9][C:8]2[C:3](=[CH:4][CH:5]=[C:6]([CH2:13][N:14]([C:15](=[O:28])[C:16]3[CH:17]=[CH:18][C:19]([CH:22]4[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]4)=[CH:20][CH:21]=3)[CH3:29])[CH:7]=2)[C:2]=1[Br:1])[CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 13388932alpha-(Trifluoromethylsulfonyloxy)hydrocinnamic acid methyl esterHCID 18505343N-(5-bromo-6-hydroxy-naphthalen-2-ylmethyl)-4-cyclohexyl-N-methyl-benzamide

Product 1

HCID 691377602-(1-Bromo-6-{[(4-cyclohexyl-benzoyl)-methyl-amino]-methyl}-naphthalen-2-yloxy)-3-phenyl-propionic acid methyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of N-(5-bromo-6-hydroxy-naphthalen-2-ylmethyl)-4-cyclohexyl-N-methyl-benzamide (799 mg, 1.51 mmol), prepared in the previous step, 3-phenyl-2-trifluoromethanesulfonyloxypropionic acid methyl ester (1.66 mmol), prepared in step 2 of Example 7, and cesium carbonate (985 mg, 3.0 mmol) in acetone was stirred at room temperature for 3 h. The reaction was partitioned between water and ethyl acetate. The aqueous layer was separated and extracted three times with ethyl acetate. The combined extracts were dried (Na2SO4) and the solvent removed under reduced pressure. Purification of the residue by column chromatography using 10%-20% ethyl acetate-hexanes as the eluent gave 2-(1-bromo-6-{[(4-cyclohexyl-benzoyl)-methyl-amino]-methyl}-naphthalen-2-yloxy)-3-phenyl-propionic acid methyl ester (445 mg, 48%), LCMS ES+(Calc'd: 613.2; Found: 614.3).

Workup

  1. customThe reaction was partitioned between water and ethyl acetate
  2. customThe aqueous layer was separated
  3. extractionextracted three times with ethyl acetate
  4. dry with materialThe combined extracts were dried (Na2SO4)
  5. customthe solvent removed under reduced pressure
  6. customPurification of the residue by column chromatography

Sources & evidence

ORD record
ord-66044f82a67b4094a48e2b8f8fdbfb30
Source dataset
uspto-grants-2003_07
Patent number
US06589970B2

Reaction notes

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