Ammonium formate → 1-{6-Hydroxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}2,2-dimethylpropan-1-one

HRID 397076Notes

Reaction equation

HRID 397076 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:21][CH:20]=1)[N:14]([C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:13][CH2:12]2)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.[OH-].[OH-].[Pd+2]>[OH:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]([C:19]1[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:23][CH:24]=1)[N:14]([C:33](=[O:38])[C:34]([CH3:36])([CH3:35])[CH3:37])[CH2:13][CH2:12]2

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 120859491-{6-Benzyloxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}-2,2-dimethylpropan-1-one

Product 1

HCID 120859431-{6-Hydroxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}2,2-dimethylpropan-1-one

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

A mixture of 1-{6-benzyloxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2yl}-2,2-dimethylpropan-1one, ammonium formate (0.033 g, 0.52 mmol), and 20% Pd(OH)2/C (0.002 g) in MeOH (10 ml) was refluxed under N2 for 1.5 hr, then filtered to remove the catalyst. The filtrate was evaporated in vacuo to a residue that was suspended in H2O (0.4 ml) and saturated NaHCO3 (0.4 ml). The aqueous mixture was extracted with CH2Cl2 (3×0.8 ml) and all of the combined organic solutions were evaporated to give the crude product. Purification by reverse-phase HPLC on a Primesphere C-18HC (50.0 mm×10.0 mm column with 5 m particle size) column, eluting with a linear gradient starting at time 0 min. of H2O:CH3CN:1% TFA/H2O (85:10:5), increasing to H2O:CH3CN:1% TFA/H2O (5:90:5) at 8 min., detected on a Micromass Platform 2 mass spectrometer (DAD 190-600 nM) gave material which, after evaporation to dryness, was purified by reverse-phase HPLC on a Primesphere C-18HC (3.0 mm×2.0 mm column with 5 m particle size) column, eluting with a linear gradient starting at time 0 min. of H2O:CH3CN:TFA (99.9:0:0.1), increasing to H2O:CH3CN:TFA (0:99.9:0.1) at 4 min., detected with a UV detector (300 nM +/−90 nM and 254 nM +/−25 nM), gave an eluent that was evaporated to dryness to give the pure product.

Workup

  1. temperaturewas refluxed under N2 for 1.5 hr
  2. filtrationfiltered
  3. customto remove the catalyst
  4. customThe filtrate was evaporated in vacuo to a residue that
  5. extractionThe aqueous mixture was extracted with CH2Cl2 (3×0.8 ml)
  6. customall of the combined organic solutions were evaporated

Sources & evidence

ORD record
ord-c0998b563ee14b7e894dfe121fc2f619
Source dataset
uspto-grants-2003_08
Patent number
US06608203B2

Reaction notes

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