Benzyl chloroformate → benzyl 1-(6-(trifluoromethyl)pyridin-3-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 445383Notes

Reaction equation

HRID 445383 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][N:18]=1.Cl[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]>C1COCC1>[F:9][C:8]([F:11])([F:10])[C:5]1[N:6]=[CH:7][C:2]([CH:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][CH2:19][N:18]2[C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])=[CH:3][CH:4]=1

Participants

6

Reactant 4

HCID 10387Benzyl chloroformateHCID 767053,4-DihydroisoquinolineHCID 27611975-Bromo-2-(trifluoromethyl)pyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 59536315benzyl 1-(6-(trifluoromethyl)pyridin-3-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-bromo-2-(trifluoromethyl)pyridine (258 mg, 1144 μmol) in THF (5 mL) at 0° C. was added isopropylmagnesium chloride (572 μL, 1144 μmmol) and the red/brown solution was stirred 2 h under N2. To a solution of 3,4-dihydroisoquinoline (75 mg, 572 μmol) in THF (2 mL) at 0° C. was added benzyl chloroformate (90 μL, 629 μmol) and the reaction was warmed to RT and stirred 15 min. The solution of Grignard reagent was added to the iminium salt and the reaction warmed to RT and stirred 1 h. The reaction was quenched with saturated NH4Cl (20 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic layers were dried (MgSO4) and concentrated to give a yellow oil. Purification by ISCO (12 g SiO2, 0-50% EtOAc/hexane) gives benzyl 1-(6-(trifluoromethyl)-pyridin-3-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate as a yellow oil.

Workup

  1. stirringstirred 15 min
  2. temperaturethe reaction warmed to RT
  3. stirringstirred 1 h
  4. customThe reaction was quenched with saturated NH4Cl (20 mL)
  5. extractionextracted with CH2Cl2 (3×20 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated
  8. customto give a yellow oil
  9. customPurification by ISCO (12 g SiO2, 0-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-9f9ee1fea73b422e90700c8ec7b05696
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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