Sodium Hydroxide → HCID 9844867, compound

HRID 1352205Notes

Reaction equation

HRID 1352205 reaction equation
[CH3:1][CH:2]([CH3:32])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[CH:20]([N:24]3[CH2:27][CH:26]([C:28]([O:30]C)=[O:29])[CH2:25]3)[CH2:19][CH2:18]4)[N:11]=2)=[CH:6][CH:5]=1.[OH-].[Na+]>CO.C(Cl)Cl.CO.Cl>[CH3:1][CH:2]([CH3:32])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[CH:20]([N:24]3[CH2:27][CH:26]([C:28]([OH:30])=[O:29])[CH2:25]3)[CH2:19][CH2:18]4)[N:11]=2)=[CH:6][CH:5]=1

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 21100039HCID 21100039, compound

Product 1

HCID 9844867HCID 9844867, compoundYield 76.9%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of 4.5 g (8.1 mmol) of methyl (±)-1-(5-(5-(4-(2-Methylpropyl)phenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3-carboxylate, Enantiomer 1 (from Example 17, Step A) in 25 mL of MeOH was treated with 3.0 mL of 5.0 N NaOH and the resulting mixture was heated at reflux for 3 h. The mixture was cooled, diluted with 4:1 v/v CH2Cl2/MeOH and neutralized with concentrated HCl. The solids were filtered and the filtrate was concentrated. Chromatography on a Biotage 75S cartridge using 4 L of 17:3 v/v CH2Cl2/MeOH+1% NH4OH, then 4 L of 3:1 v/v CH2Cl2/MeOH+1% NH4OH afforded 2.60 g of the title compound: 1H NMR (500 MHz, DMSO) δ 8.08 (d, J=8.0 Hz, 2H), 7.93 (s, 1H), 7.88 (d, J=7.5 Hz, 1H), 7.47 (d, J=7.5 Hz, 1H), 7.44 (d, J=8.0 Hz, 2H), 3.85–3.88 (m, 1H), 3.50 (app t, J=7.5 Hz, 1H), 3.39 (app d, J=7.5 Hz, 2H), 3.26 (app t, J=7.5 Hz, 1H), 3.13–3.18 (m, 1H), 2.97–3.30 (m, 1H), 2.81–2.87 (m, 1H), 2.57 (app d, J=7.5 Hz, 2H), 2.49 (t, J=1.5 Hz, 1H), 2.03–2.11 (m, 1H), 1.83–1.89 (m, 1H), 0.88 (d, J=6.5 Hz, 6H); ESI-MS 418.1 (M+H).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 3 h
  3. temperatureThe mixture was cooled
  4. filtrationThe solids were filtered
  5. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-5e9bf7dd3d814f0ab51d993fb1111794
Source dataset
uspto-grants-2007_05
Patent number
US07220734B2

Reaction notes

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