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

HRID 1942730Notes

Reaction equation

HRID 1942730 reaction equation
[CH2:1]([C:3]1[C:10]([C:11]2[N:15]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:25])[CH3:24])=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=3)[S:13][N:12]=2)=[CH:9][CH:8]=[CH:7][C:4]=1[CH:5]=O)[CH3:2].C([O-])(=O)C.[Na+].Cl.[NH:36]1[CH2:39][CH:38]([C:40]([O:42]C)=[O:41])[CH2:37]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CO>[CH2:1]([C:3]1[C:10]([C:11]2[N:15]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:24])[CH3:25])=[C:18]([C:26]([F:28])([F:29])[F:27])[CH:17]=3)[S:13][N:12]=2)=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5][N:36]1[CH2:37][CH:38]([C:40]([OH:42])=[O:41])[CH2:39]1)[CH3:2]

Participants

7

Reactant 4

HCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 21100040Methyl azetidine-3-carboxylate hydrochlorideHCID 575227002-Ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-3-yl}benzaldehyde

Product 1

HCID 575228121-[(2-Ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-3-yl}phenyl)methyl]-3-azetidinecarboxylic acidYield 36.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-3-yl}benzaldehyde (D47) (100 mg) in dichloromethane (DCM) (5 mL) and methanol (5.00 mL) was added sodium acetate (39.0 mg) and hydrogen chloride-methyl 3-azetidinecarboxylate (1:1) (72.1 mg). The reaction solution was stirred at room temperature for overnight. Sodium triacetoxyborohydride (101 mg) was added and the resulting solution was stirred at ambient temperature for 2 h. The solvent was removed in vacuo and the residue was dissolved in isopropanol/water (1:1, 5 mL), sodium hydroxide (2.378 mL) was added and the resulting solution was heated to 90° C. for 2 h. Isopropanol was removed in vacuo and the residue was acidified to pH=3-4, extracted with ethyl acetate (2*20 mL), the combined organic phases were dried over sodium sulphate and concentrated, the residue was purified by Mass Directed AutoPrep to afford 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-3-yl}phenyl)methyl]-3-azetidinecarboxylic acid (E19) (44 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.06 (3H, t), 1.27 (6H, d), 2.87 (2H, q), 3.16 (4H, m), 3.34 (1H, m), 3.60 (2H, s), 4.89 (1H, m), 7.23 (1H, t), 7.38 (1H, dd), 7.45 (1H, d), 7.65 (1H, dd), 8.18 (1H, d), 8.25 (1H, dd). δF (DMSO-d6, 376 MHz): −61.4. MS (ES): C26H26F3N3O3S requires 505. found 506.1 (M+H+).

Workup

  1. stirringthe resulting solution was stirred at ambient temperature for 2 h
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in isopropanol/water (1:1, 5 mL)
  4. additionsodium hydroxide (2.378 mL) was added
  5. temperaturethe resulting solution was heated to 90° C. for 2 h
  6. customIsopropanol was removed in vacuo
  7. extractionextracted with ethyl acetate (2*20 mL)
  8. dry with materialthe combined organic phases were dried over sodium sulphate
  9. concentrationconcentrated
  10. customthe residue was purified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-c792a6dc6037410f8d4572456adea64a
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

Loading…