Benzyl Bromide → 1-{6-Benzyloxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}-2,2,2-trifluoroethanone

HRID 397033Notes

Reaction equation

HRID 397033 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([OH:15])[CH:11]=2)[CH:6]1[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][N:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:18][CH:17]=1)=[O:4].[H-].[Na+].[CH2:34](Br)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CN(C=O)C.O>[CH2:34]([O:15][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]([C:16]1[CH:17]=[CH:18][C:19]([O:22][CH2:23][CH2:24][N:25]3[CH2:26][CH2:27][CH2:28][CH2:29]3)=[CH:20][CH:21]=1)[N:5]([C:3](=[O:4])[C:2]([F:30])([F:1])[F:31])[CH2:14][CH2:13]2)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 120859412,2,2-Trifluoro-1-{6-hydroxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}ethanone

Product 1

HCID 181723851-{6-Benzyloxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}-2,2,2-trifluoroethanoneYield 120.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

A solution of 2,2,2-trifluoro-1-{6-hydroxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}ethanone (1.886 g, 4.3 mmol) in anhydrous DMF (50 ml) was added to a suspension of NaH (0.104 g, 4.3 mmol) in anhydrous DMF (100 ml) at rt under N2. After stirring at rt for 1 hr, a solution of benzyl bromide (0.782 g, 4.6 mmol) in anhydrous DMF (10 ml) was added and the reaction mixture was heated to 100° C. for 4 hr. The reaction mixture was cooled to rt, diluted with H2O (250 ml), and extracted with EtOAc (4×100 ml). The combined extracts were washed with H2O (2×100 ml), dried over MgSO4, and concentrated in vacuo to give 2.71 g of orange oil. Purification by flash chromatography, eluting with EtOAc:MeOH (7:3) gave 0.745 g (33% yield) of yellow oil.

Workup

  1. temperaturethe reaction mixture was heated to 100° C. for 4 hr
  2. temperatureThe reaction mixture was cooled to rt
  3. extractionextracted with EtOAc (4×100 ml)
  4. washThe combined extracts were washed with H2O (2×100 ml)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7a57b3155c4a4c0992b8af35f67a4044
Source dataset
uspto-grants-2003_08
Patent number
US06608203B2

Reaction notes

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