Sodium Hydroxide → 1-{[3-(2-{3-Cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylic acid

HRID 1942744Notes

Reaction equation

HRID 1942744 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[S:14][C:15]([C:18]3[C:19]([CH2:33][CH3:34])=[C:20]([CH2:24][N:25]4[CH2:28][CH:27]([C:29]([O:31]C)=[O:30])[CH2:26]4)[CH:21]=[CH:22][CH:23]=3)=[CH:16][N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[OH-].[Na+]>C(O)(C)C.O>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[S:14][C:15]([C:18]3[C:19]([CH2:33][CH3:34])=[C:20]([CH2:24][N:25]4[CH2:26][CH:27]([C:29]([OH:31])=[O:30])[CH2:28]4)[CH:21]=[CH:22][CH:23]=3)=[CH:16][N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 66981796HCID 66981796, compound

Product 1

HCID 545769411-{[3-(2-{3-Cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylic acidYield 49.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Procedure

To a solution of methyl 1-{[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylate (D87) (126 mg) in isopropanol (40 mL) and water (10 mL) stirred under nitrogen at room temperature was added a solution of NaOH (21.2 mg) in water in one charge. The reaction mixture was stirred at room temperature overnight. Isopropanol was removed in vacuo. The residue was dissolved in water and acidified with 1N HCl to pH=5. The solvent was removed in vacuo, the residue was dissolved in THF, and filtered. The filtrate was purified by Mass Directed AutoPrep to give 1-{[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylic acid (E38) (60 mg) as a TFA salt (white solid). δH (DMSO-d6, 400 MHz): 1.05 (3H, t), 1.36 (6H, d), 2.78 (2H, d), 3.64 (1H, m), 4.27 (4H, m), 4.54 (2H, m), 4.91 (1H, m), 7.42 (4H, m), 7.87 (1H, s), 8.22 (1H, dd), 8.28 (1H, d), 10.21 (1H, br s), 13.19 (1H, br s). δF (DMSO-d6, 376 MHz): −73.6. MS (ES): C26H27N3O3S requires 461. found 462.3 (M+H+).

Workup

  1. additioncharge
  2. customIsopropanol was removed in vacuo
  3. dissolutionThe residue was dissolved in water
  4. customThe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in THF
  6. filtrationfiltered
  7. customThe filtrate was purified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-de7e4ed5f9174b84be0ecc7ce361ea1c
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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