1-Butanol → HCID 22176050, compound

HRID 1797487Notes

Reaction equation

HRID 1797487 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([OH:30])=[C:14]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:15]([CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:16]2=[O:19])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:31](O)[CH2:32][CH2:33][CH3:34].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:30][CH2:31][CH2:32][CH2:33][CH3:34])=[C:14]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:15]([CH2:20][C:21]([CH3:23])([CH3:24])[CH3:22])[C:16]2=[O:19])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 2631-ButanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 54725303HCID 54725303, compound

Product 1

HCID 22176050HCID 22176050, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-benzyloxy-2-(ethoxycarbonyl)benzoic acid (21.86 g, 120 mmol), ethyl 2-(neopentylamino)acetate (20.79 g, 120 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (28.76 g, 150 mmol) and 1-hydroxybenzotriazole (22.97 g, 150 mmol) in N,N-dimethylformamide (200 ml) was stirred at room temperature for 3 h. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (300 ml), and potassium carbonate (33.17 g, 240 mmol) and benzyl bromide (35.7 ml, 300 mmol) were added. The mixture was stirred at room temperature for 12 h. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in ethanol (50 ml) and 20% sodium ethoxide ethanol solution (34.04 g, 100 mmol) was added. The mixture was stirred at room temperature for 1 h. The reaction mixture was poured into 1N hydrochloric acid (150 ml) and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography and the component eluted earlier was concentrated to give ethyl 7-benzyloxy-4-hydroxy-2-neopentyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate as an oil. To a solution of the obtained ethyl 7-benzyloxy-4-hydroxy-2-neopentyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (3.26 g, 8 mmol), 1-butanol (1.1 ml, 12 mmol) and tributylphosphine (4.0 ml, 16 mmol) in tetrahydrofuran (30 ml) was added 1,1′-(azodicarbonyl)dipiperidine (4.04 g, 16 mmol) and the mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to give ethyl 7-benzyloxy-4-butoxy-2-neopentyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (3.61 g, 97.0%) as an oil.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-91dd6451b1b14538b86dfb5ad2f34b34
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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