Succinic anhydride → 4-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyric acid

HRID 383986Notes

Reaction equation

HRID 383986 reaction equation
[C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH2:3][CH2:2]1.CCN(CC)CC.[F:15][C:16]1[CH:25]=[C:24]2[C:19]([CH2:20][CH2:21][NH:22][CH:23]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:18][CH:17]=1.CCCCCCC>CC#N.CC(O)=O>[F:15][C:16]1[CH:25]=[C:24]2[C:19]([CH2:20][CH2:21][N:22]([C:1](=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=[O:5])[CH:23]2[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 7922Succinic anhydrideHCID 8471TriethylamineHCID 8900HeptaneHCID 67369877HCID 67369877, compound

Product 1

HCID 685597314-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyric acidYield 37.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent

Procedure

5.0 g (49.7 mmol) of succinic anhydride and 4.0 ml (28.4 mmol) of NEt3 were added in succession to a solution of the crude product 7-fluoro-1-phenyl-1,2,3,4-tetrahydroisoquinoline (max. 14.2 mmol) in MeCN (200 ml) and the mixture was stirred for 16 h at RT. It was then concentrated to small volume under vacuum and the residue was taken up with a saturated aqueous NaHCO3 solution (300 ml). It was extracted with DCM (2×200 ml). The combined organic phases were washed with a 1M aqueous hydrochloric acid (200 ml), dried over Na2SO4, filtered and concentrated to small volume under vacuum. Column chromatography (heptane/EE 1:1+1% AcOH) of the residue produced 1.72 g (5.3 mmol, 10% over 3 stages) of 4-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyric acid.

Workup

  1. concentrationIt was then concentrated to small volume under vacuum
  2. extractionIt was extracted with DCM (2×200 ml)
  3. washThe combined organic phases were washed with a 1M aqueous hydrochloric acid (200 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to small volume under vacuum

Sources & evidence

ORD record
ord-2baaa6b81dee49bcb349d4bf208483b0
Source dataset
uspto-grants-2013_02
Patent number
US08367700B2

Reaction notes

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