Dimethylformamide → HCID 86723738, compound

HRID 577513Notes

Reaction equation

HRID 577513 reaction equation
[CH3:1][C:2]1[C:3]([C:13]([O:15]C)=[O:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.[H-].[Na+].Cl[CH2:20][C:21]1[C:26]([CH3:27])=[CH:25][C:24](C)=[CH:23][C:22]=1[O:29][CH2:30][C:31]1[C:36](C2(OCC3C=CC=CC=3)C=C(C)C=C(C)C2CCl)=[CH:35][CH:34]=[CH:33][CH:32]=1.C[N:56](C=O)C>>[CH2:30]([O:29][C:22]1[C:21]([CH2:20][N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[C:2]([CH3:1])[C:3]([C:13]([OH:15])=[O:14])=[CH:4][CH:5]=3)[C:10]2=[O:12])=[C:26]([CH3:27])[CH:25]=[C:24]([CH3:23])[N:56]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 86723739HCID 86723739, compoundHCID 86723740HCID 86723740, compound

Product 1

HCID 86723738HCID 86723738, compoundYield 61%

Conditions

Temperature
0 °C

Procedure

To a stirred solution of methyl 8-methyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-7-carboxylate (76d, 100 mg, 0.46 mmol) in DMF (5 mL) was added NaH (0.032 g, 1.32 mmol, 60% in oil) at 0° C. under N2. After stirring at 0° C. for 30 minutes, 1-(benzyloxy)-2-(chloromethyl)-3,5-dimethylbenzene benzyl 2-(chloromethyl)-3,5-dimethylphenyl ether (Cpd Z, 180 mg, 0.69 mmol) was added and the reaction mixture stirred at room temperature overnight. The reaction mixture was poured into ice-water (20 mL). The reaction mixture was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (2×10 mL), dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc=1:1) to obtain 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-methyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid (76e, 120 mg, 61%) as a yellow gum.

Workup

  1. stirringthe reaction mixture stirred at room temperature overnight
  2. extractionThe reaction mixture was extracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with brine (2×10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by column chromatography (petroleum ether/EtOAc=1:1)

Sources & evidence

ORD record
ord-34cc9efdd8ad41a5a9cb381859a5e990
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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