Dimethylamine, hydrochloride → tert-Butyl 6-[({4'-[2-(dimethylamino)-2-oxoethyl]-1,1'-biphenyl-4-yl}oxy)methyl]-2-hydroxy-3-(trifluoromethyl)benzoate

HRID 2076661Notes

Reaction equation

HRID 2076661 reaction equation
Cl.[CH3:2][NH:3][CH3:4].Cl.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1.[C:27]([O:31][C:32]([C:34]1[C:57]([OH:58])=[C:56]([C:59]([F:62])([F:61])[F:60])[CH:55]=[CH:54][C:35]=1[CH2:36][O:37][C:38]1[CH:43]=[CH:42][C:41]([C:44]2[CH:49]=[CH:48][C:47]([CH2:50][C:51](O)=[O:52])=[CH:46][CH:45]=2)=[CH:40][CH:39]=1)=[O:33])([CH3:30])([CH3:29])[CH3:28].[Cl-].[NH4+]>C(#N)C.C(N(CC)CC)C>[CH3:2][N:3]([CH3:4])[C:51](=[O:52])[CH2:50][C:47]1[CH:48]=[CH:49][C:44]([C:41]2[CH:42]=[CH:43][C:38]([O:37][CH2:36][C:35]3[C:34]([C:32]([O:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:33])=[C:57]([OH:58])[C:56]([C:59]([F:62])([F:61])[F:60])=[CH:55][CH:54]=3)=[CH:39][CH:40]=2)=[CH:45][CH:46]=1

Participants

8

Reactant 5

HCID 10473Dimethylamine, hydrochlorideHCID 25517Ammonium ChlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11555148HCID 11555148, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 86617416tert-Butyl 6-[({4'-[2-(dimethylamino)-2-oxoethyl]-1,1'-biphenyl-4-yl}oxy)methyl]-2-hydroxy-3-(trifluoromethyl)benzoateYield 171.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

Dimethylamine hydrochloride (41 mg, 0.502 mmol), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (96 mg, 0.50 mmol), hydroxybenzotriazole (77 mg, 0.50 mmol) and triethylamine (0.10 ml) were added to a solution of (4′-{[2-(tert-butoxycarbonyl)-3-hydroxy-4-(trifluoromethyl)benzyl]oxy}-1,1′-biphenyl-4-yl)acetic acid (168 mg, 0.334 mmol) obtained in Example (7) in acetonitrile (10 ml). After the mixture was stirred for 10 hours, a saturated aqueous ammonium chloride solution was added thereto and the mixture was extracted with ethyl acetate. The organic layer was successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: hexane/ethyl acetate=3/1-methylene chloride/methanol=15/1) to give the title compound as a pale yellow crystal (303 mg, yield: 34%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was successively washed with water
  3. dry with materiala saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
  4. customThe residue obtained
  5. customby removing the solvent under reduced pressure
  6. customwas purified by silica gel column chromatography (eluting solvent: hexane/ethyl acetate=3/1-methylene chloride/methanol=15/1)

Sources & evidence

ORD record
ord-698c1e9930ea4b8b9cc0ede72cb0b40a
Source dataset
uspto-grants-2011_04
Patent number
US07923573B2

Reaction notes

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