Sodium hydride → 2,2,2-Trifluoro-1-{6-methoxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}ethanone

HRID 397073Notes

Reaction equation

HRID 397073 reaction equation
[F:1][C:2]([F:25])([F:24])[C:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:15][CH3:16])[CH:11]=2)[CH:6]1[C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1)=[O:4].[H-].[Na+].Cl.Cl[CH2:30][CH2:31][N:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1>CN(C=O)C.O>[F:25][C:2]([F:1])([F:24])[C:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:15][CH3:16])[CH:11]=2)[CH:6]1[C:17]1[CH:18]=[CH:19][C:20]([O:23][CH2:30][CH2:31][N:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)=[CH:21][CH:22]=1)=[O:4]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 120859392,2,2-trifluoro-1-[1-(4-hydroxyphenyl)-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]ethanone

Product 1

HCID 120859402,2,2-Trifluoro-1-{6-methoxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}ethanoneYield 87.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

A solution of 2,2,2-trifluoro-1-[1-(4-hydroxyphenyl)-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]ethanone (18.98 g, 54.0 mmol) in anhydrous DMF (200 ml) was added to a suspension of NaH (2.592 g, 108.0 mmol) in anhydrous DMF (400 ml) at rt under N2. After stirring at rt for 1 hr, a solution of 1-(2-chloroethyl)pyrrolidine hydrochloride (9.184 g, 54.0 mmol) in anhydrous DMF (200 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 (2000 ml), and extracted with EtOAc (4×250 ml). The combined extracts were washed with H2O (3×250 ml), dried over MgSO4, and concentrated in vacuo to give 21.15 g of yellow oil. Purification by flash chromatography, eluting with EtOAc:MeOH (8:2) gave 10.503 g (43% 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 (4×250 ml)
  4. washThe combined extracts were washed with H2O (3×250 ml)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6cdbae25dc1e42ec8b1ace292ea04137
Source dataset
uspto-grants-2003_08
Patent number
US06608203B2

Reaction notes

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