Toluene → 6-(4-Cyano-phenoxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 228474Notes

Reaction equation

HRID 228474 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([OH:18])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].F[C:33]1[CH:40]=[CH:39][C:36]([C:37]#[N:38])=[CH:35][CH:34]=1>CC(N(C)C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][C:33]3[CH:40]=[CH:39][C:36]([C:37]#[N:38])=[CH:35][CH:34]=3)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 145174-FluorobenzonitrileHCID 10060623tert-Butyl 6-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 597299906-(4-Cyano-phenoxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterYield 91.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Combine in a round bottom flask equipped with a Dean Stark Trap 6-Hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.59 g, 6.36 mmol), toluene, dimethylacetamide (10 ml and 30 ml respectively), K2CO3 (1.25 g, 9.04 mmol), and 4-Fluorobenzonitrile (0.72 g, 6.04 mmol). Reflux the reaction under a Nitrogen atmosphere for 4 hours then cool to room temperature. Add water to the reaction mixture and extract the product from the water layer using ethyl acetate. The product, a white solid, precipitates out from the ethyl acetate to afford 1.93 g, 5.5 mmol (87% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 1.5 (9H, s), 2.75-2.85 (2H, m), 3.6-3.7 (2H, m), 4.5 (2H, s), 6.8-6.9 (2H, m), 6.9-7.0 (2H, m), 7.1-7.2 (1H, m), 7.5-7.6 (2H, m); MS m/z 249 (M+).

Workup

  1. temperatureReflux
  2. customthe reaction under a Nitrogen atmosphere for 4 hours
  3. extractionAdd water to the reaction mixture and extract the product from the water layer
  4. customThe product, a white solid, precipitates out from the ethyl acetate

Sources & evidence

ORD record
ord-3bee98cb223b4d3bae19bc5b29f374ee
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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