Lithium Hydroxide → HCID 68887882, compound

HRID 1821026Notes

Reaction equation

HRID 1821026 reaction equation
[OH-].[Li+].[Cl:3][C:4]1[CH:5]=[C:6]([C:14]2[O:18][N:17]=[C:16]([C:19]3[C:20]([CH3:32])=[C:21]4[C:25](=[CH:26][CH:27]=3)[CH2:24][CH:23]([C:28]([O:30]C)=[O:29])[CH2:22]4)[N:15]=2)[CH:7]=[N:8][C:9]=1[O:10][CH:11]([CH3:13])[CH3:12]>C1COCC1.O>[Cl:3][C:4]1[CH:5]=[C:6]([C:14]2[O:18][N:17]=[C:16]([C:19]3[C:20]([CH3:32])=[C:21]4[C:25](=[CH:26][CH:27]=3)[CH2:24][CH:23]([C:28]([OH:30])=[O:29])[CH2:22]4)[N:15]=2)[CH:7]=[N:8][C:9]=1[O:10][CH:11]([CH3:12])[CH3:13]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 68892018HCID 68892018, compound

Product 1

HCID 68887882HCID 68887882, compoundYield 92.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Lithium hydroxide (3.3 mg, 0.0795 mmol) was added to a solution of methyl 5-(5-(5-chloro-6-isopropoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl)-4-methylindane-2-carboxylate (17.0 mg, 0.0397 mmol, from Step G) in THF (1.0 mL) and H2O (300 μL) and heated to 50° C. After 30 min, the reaction mixture was concentrated in vacuo and partitioned between EtOAc (5 mL) and 5% citric acid (2 mL). The layers were separated and organic layer was washed with H2O (3×2 mL), brine (1×2 mL) and dried over MgSO4. The mixture was filtered and the filtrated concentrated in vacuo. Purification of the residue by flash chromatography (3% CH3OH/CH2Cl2/1% HCO2H) on SiO2 afforded 15.2 mg of the title compound as a white solid: 1H NMR (500 MHz, CD3OD) δ 1.41 (d, 6H, J=6.2 Hz), 2.51 (s, 3H), 3.19-3.41 (m, 5H), 5.49 (septet, 1H, J=6.2 Hz), 7.17 (d, 1H, J=8.0 Hz), 7.78 (d, 1H, J=7.8 Hz), 8.39 (s, 1H), 8.83 (s, 1H); HPLC A: rt=4.11 min, m/z=414.3 (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. custompartitioned between EtOAc (5 mL) and 5% citric acid (2 mL)
  3. customThe layers were separated
  4. washorganic layer was washed with H2O (3×2 mL), brine (1×2 mL)
  5. dry with materialdried over MgSO4
  6. filtrationThe mixture was filtered
  7. concentrationthe filtrated concentrated in vacuo
  8. customPurification of the residue by flash chromatography (3% CH3OH/CH2Cl2/1% HCO2H) on SiO2

Sources & evidence

ORD record
ord-0542ab66114745118a5f01f3d44eef6c
Source dataset
uspto-grants-2009_10
Patent number
US07605171B2

Reaction notes

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