Sodium Hydroxide → HCID 44548889, compound

HRID 1512920Notes

Reaction equation

HRID 1512920 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[NH:24][CH:23]=[C:22]4[CH2:26][CH2:27][NH:28][CH2:29][CH2:30][C:31]([O:33]CC)=[O:32])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>O1CCCC1.CO.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[NH:24][CH:23]=[C:22]4[CH2:26][CH2:27][NH:28][CH2:29][CH2:30][C:31]([OH:33])=[O:32])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 59146183HCID 59146183, compound

Product 1

HCID 44548889HCID 44548889, compoundYield 74.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of ethyl N-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]ethyl}-β-alaninate (D85) (186 mg) in tetrahydrofuran (5 mL) and methanol (5 mL) stirred at 20° C. was added a solution of sodium hydroxide (40 mg) in water (5 mL) in one charge. The reaction mixture was stirred at 20° C. overnight. The reaction mixture was concentrated to about 5 mL and then HCl aquous solution was added dropwise until no further white precipitate was formed. The solid was filtered and washed with EtOAc. The solid was collected and then was suspended in methanol (5 mL) and water (5 mL). The mixture was acidified with HCl aquous solution to pH around 1 to form a clear solution. After most of the solvent was evaporated off, the residue was freeze-dried to afford N-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]ethyl}-β-alanine (E62) (130 mg) as a hydrochloride salt. δH (DMSO-d6, 400 MHz): 1.38 (6H, d), 2.70 (2H, t), 3.12-3.29 (4H, m), 3.33 (2H, m), 4.88-4.94 (1H, m), 7.27 (1H, t), 7.41 (1H, d), 7.47 (1H, d), 7.90 (1H, d), 7.99 (1H, dd), 8.22 (1H, dd), 8.39 (1H, d), 8.71 (1H, br), 11.03 (1H, br s), 12.70 (1H, br s). MS (ES): C24H26ClN4O4 requires 468; found 469.2 (M+H+).

Workup

  1. additioncharge
  2. concentrationThe reaction mixture was concentrated to about 5 mL
  3. additionHCl aquous solution was added dropwise until no further white precipitate
  4. customwas formed
  5. filtrationThe solid was filtered
  6. washwashed with EtOAc
  7. customThe solid was collected
  8. customto form a clear solution
  9. customAfter most of the solvent was evaporated off
  10. customthe residue was freeze-dried

Sources & evidence

ORD record
ord-5b2c55475fe148ac836019d56bb78ebe
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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