Lithium Hydroxide → HCID 16222912, compound

HRID 856984Notes

Reaction equation

HRID 856984 reaction equation
[Li+].[OH-].C[O:4][C:5](=[O:29])[CH2:6][CH2:7][CH2:8][N:9]([C:11]1[CH:16]=[C:15]([C:17]2[N:21]=[C:20]([C:22]3[S:23][CH:24]=[CH:25][C:26]=3[Cl:27])[O:19][N:18]=2)[CH:14]=[CH:13][C:12]=1[Cl:28])[CH3:10]>O.C1COCC1>[Cl:28][C:12]1[CH:13]=[CH:14][C:15]([C:17]2[N:21]=[C:20]([C:22]3[S:23][CH:24]=[CH:25][C:26]=3[Cl:27])[O:19][N:18]=2)=[CH:16][C:11]=1[N:9]([CH3:10])[CH2:8][CH2:7][CH2:6][C:5]([OH:29])=[O:4]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 16222911HCID 16222911, compound

Product 1

HCID 16222912HCID 16222912, compoundYield 84.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of LiOH (0.280 g, 6.66 mmol) in H2O (6.0 mL) was added over 1 minute to a solution of 4-({2-chloro-5-[5-(3-chlorothiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-methyl-amino)-butyric acid methyl ester (2.03 g, 4.76 mmol) in THF (55.0 mL) at 0° C. The ice bath was removed and the solution was allowed to equilibrate to room temperature at which point THF (20.0 mL) was added. The resulting suspension was stirred for 21 h and then EtOH (10 mL) was added and the solution was stirred for 10.5 h. The reaction solution was then diluted with 3M NaOH (1.05 mL) and EtOH (3.0 mL) and stirred for 30 min. The solution was diluted with dichloromethane (100 mL), washed with aqueous NaHCO3 (50 mL), and the solvent was removed by rotary evaporation. The residue was purified by flash column chromatography (silica gel, gradient elution using dichloromethane then EtOAc) to give 1.65 g (84%) of the title compound as a white solid. 1H NMR (CDCl3): 7.86 (d, 1H, J=1.9 Hz), 7.76 (dd, 1H, J=8.2 and 1.9 Hz), 7.60 (d, 1H, J=5.2 Hz), 7.49 (d, 1H, J=8.2 Hz), 7.14 (d, 1H, J=5.5 Hz), 3.16 (t, 2H, J=7.0 Hz), 2.85 (s, 3H), 2.48 (t, 3H, J=7.3 Hz), 2.02–1.92 (m, 2H).

Workup

  1. customThe ice bath was removed
  2. customto equilibrate to room temperature at which point THF (20.0 mL)
  3. additionwas added
  4. additionEtOH (10 mL) was added
  5. stirringthe solution was stirred for 10.5 h
  6. additionThe reaction solution was then diluted with 3M NaOH (1.05 mL) and EtOH (3.0 mL)
  7. stirringstirred for 30 min
  8. additionThe solution was diluted with dichloromethane (100 mL)
  9. washwashed with aqueous NaHCO3 (50 mL)
  10. customthe solvent was removed by rotary evaporation
  11. customThe residue was purified by flash column chromatography (
  12. washsilica gel, gradient elution

Sources & evidence

ORD record
ord-666cd3e0b22d4409b8c5f416794e363b
Source dataset
uspto-grants-2006_12
Patent number
US07144876B2

Reaction notes

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