Hydrochloric Acid → 1-(3-(5-(3-Chloro-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2-ethylbenzyl)azetidine-3-carboxylic acid

HRID 1942710Notes

Reaction equation

HRID 1942710 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:32][CH3:33])=[C:19]([CH2:23][N:24]4[CH2:27][CH:26]([C:28]([O:30]C)=[O:29])[CH2:25]4)[CH:20]=[CH:21][CH:22]=3)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+].Cl>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:32][CH3:33])=[C:19]([CH2:23][N:24]4[CH2:25][CH:26]([C:28]([OH:30])=[O:29])[CH2:27]4)[CH:20]=[CH:21][CH:22]=3)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58494145HCID 58494145, compound

Product 1

HCID 584940121-(3-(5-(3-Chloro-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2-ethylbenzyl)azetidine-3-carboxylic acidYield 19.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

To a solution of crude methyl 1-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylate (D13) (54 mg) in isopropanol (3 mL) and water (3 mL) was added sodium hydroxide (50 mg). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was neutralized with 2N HCl till pH ˜6.0. The mixture was extracted with EA/THF for 3 times. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate. The dried solution was concentrated and the residue was purified by Mass Directed AutoPrep (basic conditions) to give 1-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylic acid (E4) (10 mg) as a TFA salt (off-white solid). δH (DMSO-d6, 400 MHz): 1.09 (3H, t), 1.35 (6H, d), 2.89 (2H, m), 3.61 (2H, m), 4.28 (3H, br. s.), 4.53 (2H, m), 4.84 (1H, m), 7.38 (1H, d), 7.44 (1H, m), 7.58 (2H, m), 7.96 (1H, dd), 8.10 (1H, d), 13.06 (1H, br s). δF (DMSO-d6, 376 MHz): −73.4. MS (ES): C24H26ClN3O3S requires 471. found 472.1 (M+H+).

Workup

  1. extractionThe mixture was extracted with EA/THF for 3 times
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationThe dried solution was concentrated
  5. customthe residue was purified by Mass Directed AutoPrep (basic conditions)

Sources & evidence

ORD record
ord-1bd480bca3164327b1bdcfcddff01aa6
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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