Trifluoroacetic acid → 3-[6-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid tert-butyl ester

HRID 2374448

Reaction equation

HRID 2374448 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([C:27]([F:30])([F:29])[F:28])[CH:21]=3)[CH:14]=2)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C.[C:47]([O:51][C:52](=[O:55])[CH:53]=[CH2:54])([CH3:50])([CH3:49])[CH3:48]>C(Cl)Cl>[C:47]([O:51][C:52](=[O:55])[CH2:53][CH2:54][N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([C:27]([F:29])([F:28])[F:30])[CH:21]=3)[CH:14]=2)[CH2:9]1)([CH3:50])([CH3:49])[CH3:48]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 15458tert-Butyl acrylateHCID 81531DiisopropylethylamineHCID 691462886-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Product 1

HCID 691740893-[6-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (70 mg, 0.158 mmol) in CH2Cl2 (1 mL) is added TFA(1 mL). The mixture is stirred at room temperature for 30 minutes. All the solvents are removed under reduced pressure. The mixture is dissolved in CH3OH (1.5 mL). Then DIEA (269 μL, 10 eq.) and acrylic acid tert-butyl ester (46 μL, 2 eq.) are added. The mixture is heated to 90° C. for 20 minutes using microwave irradiation. All the solvent is evaporated and the mixture is purified by column chromatography (silica gel, EtOAc/Hexane, gradient) to give 56 mg of 3-[6-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid tert-butyl ester.

Workup

  1. customAll the solvents are removed under reduced pressure
  2. dissolutionThe mixture is dissolved in CH3OH (1.5 mL)
  3. temperatureThe mixture is heated to 90° C. for 20 minutes
  4. custommicrowave irradiation
  5. customAll the solvent is evaporated
  6. customthe mixture is purified by column chromatography (silica gel, EtOAc/Hexane, gradient)

Sources & evidence

ORD record
ord-be0b16d5f18f4fc5b2a5e073d6350a0a
Source dataset
uspto-grants-2008_12
Patent number
US07462629B2

Linked notes

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