Hydrochloric Acid → 1-[(2-Ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-3-azetidinecarboxylic acid

HRID 1942709Notes

Reaction equation

HRID 1942709 reaction equation
[CH2:1]([C:3]1[C:8]([C:9]2[S:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([CH3:23])[CH3:22])=[C:16]([C:24]([F:27])([F:26])[F:25])[CH:15]=3)=[N:12][N:13]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:28][N:29]1[CH2:32][CH:31]([C:33]([O:35]C)=[O:34])[CH2:30]1)[CH3:2].[OH-].[Na+].Cl>C(O)(C)C.O>[CH2:1]([C:3]1[C:8]([C:9]2[S:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([CH3:23])[CH3:22])=[C:16]([C:24]([F:27])([F:26])[F:25])[CH:15]=3)=[N:12][N:13]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:28][N:29]1[CH2:30][CH:31]([C:33]([OH:35])=[O:34])[CH2:32]1)[CH3:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66981848Methyl 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-3-azetidinecarboxylate

Product 1

HCID 545789141-[(2-Ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-3-azetidinecarboxylic acidYield 56.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

To a solution of methyl 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-3-azetidinecarboxylate (D8) (64 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 to give 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-3-azetidinecarboxylic acid (E2) (35 mg) as an off-white solid. δH (DMSO-d6, 400 MHz): 1.10 (3H, t), 1.33 (6H, d), 2.85 (2H, m), 3.23 (3H, m), 3.42 (2H, m), 3.67 (2H, s), 4.93 (1H, m), 7.33 (1H, t), 7.50 (3H, m), 8.23 (2H, m). δF (DMSO-d6, 376 MHz): −61.3. MS (ES): C25H26F3N3O3S requires 505. found 506.2 (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

Sources & evidence

ORD record
ord-d9929c8b59a54bdc8a89895bbcca9423
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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