Potassium Carbonate → tert-butyl 3-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)propanoate

HRID 2403220Notes

Reaction equation

[C:1]([C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][NH:9][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].C([O-])([O-])=O.[K+].[K+].Br[CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23]>CC#N>[C:1]([C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][N:9]([CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:10]2)=[CH:5][CH:4]=1)#[N:2]

Participants

Conditions

Temperature: 70 °C

Procedure

7-Cyano-1,2,3,4-tetrahydroisoquinoline (7 g; 44.25 mmol; 1 eq.) and K2CO3 (7.34 g; 53.1 mmol; 1.2 eq) were suspended in CH3CN (280 mL). tert-Butyl 3-bromopropionate (7.77 mL; 46.46 mmol; 1.05 eq.) was added. The reaction mixture was heated to 70° C. for 24 hours. As the reaction was not complete, tert-butyl 3-bromopropionate (3.70 mL; 22.12 mmol; 0.50 eq.) and K2CO3 (3.06 g; 22.12 mmol; 0.5 eq) were added and the mixture was stirred at 70° C. for additional 48 hours. Solvents were removed under vacuum and the solid residue was partitioned between NaHCO3 sat (100 mL) and EtOAc (200 mL). The organic layer was then washed with brine and dried over magnesium to give the title compound as a yellow oil (11.9 g; 93.9%). It was used in the next step without further purification. 1H NMR: (DMSO-d6, 400 MHz) δ 7.57-7.54 (m, 2H), 7.32-7.29 (m, 1H), 3.59 (s, 2H), 2.87-2.83 (t, J=5.94 Hz, 2H), 2.74-2.66 (m, 4H), 2.46-2.42 (t, J=7.01 Hz, 2H), 1.39 (s, 9H). HPLC/MS: 287.1 (M+H)+. HPLC (Method A) Rt 2.37 min (Purity: 96.4%).

Workup

customSolvents were removed under vacuum
customthe solid residue was partitioned between NaHCO3
washThe organic layer was then washed with brine
dry with materialdried over magnesium

Sources & evidence

ORD record: ord-3120afe7e1f549d1880d3e42cd0934b8
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802663B2

Reaction notes

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