Hydrochloric Acid → (S)-4-(1-(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzoic acid tromethamine salt

HRID 1892745Notes

Reaction equation

HRID 1892745 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([CH3:32])[C:22]=1[N:23]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[N:24]1)[O:5][C@H:6]([C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=[O:15])=[CH:12][CH:11]=1)[CH2:7][CH2:8][CH3:9].[OH-].[Na+].Cl.[CH2:36]([OH:43])[C:37]([NH2:42])([CH2:40][OH:41])[CH2:38][OH:39]>O.CO>[NH2:42][C:37]([CH2:40][OH:41])([CH2:38][OH:39])[CH2:36][OH:43].[CH3:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([CH3:32])[C:22]=1[N:23]1[CH:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[N:24]1)[O:5][C@H:6]([C:10]1[CH:11]=[CH:12][C:13]([C:14]([OH:16])=[O:15])=[CH:18][CH:19]=1)[CH2:7][CH2:8][CH3:9]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6503Tris(hydroxymethyl)aminomethaneHCID 14798Sodium HydroxideHCID 68156304(S)-methyl 4-(1-(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzoate

Product 1

HCID 68157375(S)-4-(1-(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzoic acid tromethamine saltYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
35 °C

Procedure

To the solution from step 3 was added 5 M sodium hydroxide solution (29 mL, 145 mmol) and methanol (30 mL). The solution was heated to 35° C. for 6 h. After cooling to room temperature, the solution was acidified with conc. HCl (12.4 mL). The reaction was washed with water (30 mL). The organic solution was concentrated and the residue taken up in acetonitrile (100 mL). A solution of tris(hydroxymethyl)aminomethane (5.82 g, 48 mmol) in water (5 mL) was added slowly. The resulting slurry was cooled to 0° C. The product was filtered and washed with acetonitrile to give the desired salt as a white solid (20.5 g, 77% yield) 1H NMR (400 MHz, DMSO-d6) δ: 8.53 (s, 1H), 8.09 (s, 1H), 7.80 (d, J=8.2 Hz, 2H), 7.35 (d, J=8.2 Hz, 2H), 6.74 (s, 2H), 5.38 (dd, J=7.4, 5.1 Hz, 1H), 3.37 (s, 6H), 1.94-1.85 (m, 1H), 1.79 (s, 6H), 1.76-1.68 (m, 1H), 1.45-1.29 (m, 2H), 0.89 (t, J=7.5 Hz, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. washThe reaction was washed with water (30 mL)
  3. concentrationThe organic solution was concentrated
  4. temperatureThe resulting slurry was cooled to 0° C
  5. filtrationThe product was filtered
  6. washwashed with acetonitrile

Sources & evidence

ORD record
ord-a857422c079f4385b1a07201bf32425b
Source dataset
uspto-grants-2013_08
Patent number
US08507533B2

Reaction notes

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