Benzene → Ethyl 4-(2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)butanoate

HRID 1444691Notes

Reaction equation

HRID 1444691 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH2:7]2.C(Cl)Cl.C1C=CC=CC=1.[Br-].[CH2:28]([O:30][C:31](=[O:36])[CH2:32][CH2:33][CH2:34][Zn+])[CH3:29]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:14][C:13]([F:16])([F:15])[C:12]([N:6]1[CH2:5][CH2:4][C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[CH2:34][CH2:33][CH2:32][C:31]([O:30][CH2:28][CH3:29])=[O:36])[CH2:7]1)=[O:17]

Participants

7

Reactant 4

HCID 241BenzeneHCID 6344DichloromethaneHCID 184142741-(5-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethanoneHCID 178471550HCID 178471550, compound

Product 1

HCID 58597314Ethyl 4-(2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)butanoate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-(5-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethanone (4.0 g, 13 mmol) and Pd(dppf)Cl2.CH2Cl2 (530 mg, 0.65 mmol) was azeotroped with benzene and suspended in 50 mL of dry THF. At room temperature, 4-ethoxy-4-oxobutylzinc bromide (0.5M in THF, 52 mL, 26 mmol) was added dropwise with syringe. The orange suspension became a clear brown solution. The reaction mixture was then refluxed for 1 h. After cooling to room temperature, it was quenched with brine, extracted with EtOAc, washed with 10% HCl and brine, dried over Na2SO4, and evaporated to dryness. Flash chomatography (SiO2, EtOAc/hexane=15:100 to 20:100) gave ethyl 4-(2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)butanoate as a white solid.

Workup

  1. temperatureThe reaction mixture was then refluxed for 1 h
  2. customit was quenched with brine
  3. extractionextracted with EtOAc
  4. washwashed with 10% HCl and brine
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-5fb8438bee324fc59ba4652a5bb9d5ce
Source dataset
uspto-grants-2010_02
Patent number
US07662811B2

Reaction notes

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