N-methyl-2-pyrrolidone → HCID 86623625, compound

HRID 1821024Notes

Reaction equation

HRID 1821024 reaction equation
FC(F)(F)S(O[C:7]1[C:8]([CH3:21])=[C:9]2[C:13](=[CH:14][CH:15]=1)[C@@H:12]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[CH2:11][CH2:10]2)(=O)=O.[CH3:24][N:25]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:24]([C:7]1[C:8]([CH3:21])=[C:9]2[C:13](=[CH:14][CH:15]=1)[C@@H:12]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[CH2:11][CH2:10]2)#[N:25]

Participants

6

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 86623624HCID 86623624, compound

Product 1

HCID 86623625HCID 86623625, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

To a solution of methyl (R or S)-(5-Trifluoromethylsulfonyloxy-4-methyl-indan-1-yl)acetate (1.00 g, 2.84 mmol, from Step I) in N-methylpyrrolidinone (13 mL) under argon, zinc cyanide (267 mg, 2.27 mmol), Pd2 dba3 (13.0 mg, 14.2 μmol) and dppf (19.0 mg, 34.1 μmol) and the reaction mixture was heated to 100° C. After 16 hr, the reaction mixture was concentrated in vacuo and partitioned between EtOAc and H2O. The layers were separated and the organic layer was washed with H2O, brine and dried over MgSO4. The mixture was filtered, the filtrate concentrated in vacuo, and the residue purified by flash chromatography (5, 10% EtOAc/hexanes) on SiO2 to give 553 mg of the title compound as a white solid: 1H NMR (500 MHz, CDCl3) δ 1.76-1.80 (m, 1H), 2.41-2.50 (m, 5H), 2.73 (dd, 1H, J=5.8, 15.8 Hz), 2.78-2.84 (m, 1H), 2.91 (ddd, 1H, J=4.8, 8.7, 13.5 Hz) 3.61-3.67 (m, 1H), 3.71, (s, 3H), 7.07 (d, 1H, J=7.8 Hz), 7.43 (d, 1H, J=7.7 Hz).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. custompartitioned between EtOAc and H2O
  3. customThe layers were separated
  4. washthe organic layer was washed with H2O, brine
  5. dry with materialdried over MgSO4
  6. filtrationThe mixture was filtered
  7. concentrationthe filtrate concentrated in vacuo
  8. customthe residue purified by flash chromatography (5, 10% EtOAc/hexanes) on SiO2

Sources & evidence

ORD record
ord-9175e79a2ffa4a1eb58b37d0a827458c
Source dataset
uspto-grants-2009_10
Patent number
US07605171B2

Reaction notes

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