Sodium Carbonate → tert-Butyl 6-[2-(trifluoromethyl)pyrimidin-5-yl]-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 643490Notes

Reaction equation

HRID 643490 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH2:15][N:14]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:13][CH2:12]3)O1.CC1(C)C(C)(C)OB(C2C=CC=C3C=2CN(C(OC(C)(C)C)=O)CC3)O1.FC(F)(F)S(O[C:59]1[CH:60]=[N:61][C:62]([C:65]([F:68])([F:67])[F:66])=[N:63][CH:64]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd]Cl.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.[Fe+2].CCO.C1(C)C=CC=CC=1>[F:66][C:65]([F:68])([F:67])[C:62]1[N:63]=[CH:64][C:59]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH2:15][N:14]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:13][CH2:12]3)=[CH:60][N:61]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 52987621(2-(Tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-YL)boronic acid pinacol esterHCID 66734880tert-butyl 8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 866151602-(Trifluoromethyl)pyrimidin-5-yl trifluoromethanesulfonate

Product 1

HCID 86618203tert-Butyl 6-[2-(trifluoromethyl)pyrimidin-5-yl]-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 48%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
81 °C

Procedure

A 4:1 mixture (0.10 g, 0.28 mmol) of tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate and tert-butyl 8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 2-(trifluoromethyl)pyrimidin-5-yl trifluoromethanesulfonate (0.083 g, 0.28 mmol), PdCl2×dppf (0.0048 g), 2M sodium carbonate (1.1 mL), toluene (4.0 mL) and EtOH (1.0 mL) was purged with dry argon for ten minutes then heated in a sealed vial at 81° C. for 6 h. The black solution was filtered through glass-wool, taken up in water-brine and washed twice with EtOAc. The combined organic phases were dried, filtered and concentrated with silica (5 g). Column chromatography with EtOAc-heptanes (1:8 through 1:5) gave 0.051 g (48%) of the title product as white solid.

Workup

  1. filtrationThe black solution was filtered through glass-wool
  2. washwashed twice with EtOAc
  3. customThe combined organic phases were dried
  4. filtrationfiltered
  5. concentrationconcentrated with silica (5 g)

Sources & evidence

ORD record
ord-0f4ce333f5df48ef9496b5ec8fb34983
Source dataset
uspto-grants-2010_04
Patent number
US07700604B2

Reaction notes

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